Day One for the $68 billion combination of Pfizer Inc. and Wyeth was Oct. 16, a Friday, but for researchers at the 20 R&D centers the two pharma companies were operating around the world, the mood probably wasn't TGIF. True, they could finally get a look at what their counterparts were working on, which is usually exciting for scientists. The backdrop to any scholarly sharing, however, was a plan to consolidate those 20 centers into five central hubs, cutting about 2,000 jobs and as much as $3 billion in spending. Talk about a high-pressure peer review.

The Pfizer-Wyeth layoffs, expected to ­total 19,500 across both companies, may seem like especially bad news, since they come at a time of painfully high unemployment. But of course, M&A and layoffs are often linked. Nobody knows this better than corporate dealmakers who, far more than bankers or lawyers, must live with the results of their transactions. For most of them it goes without saying that job cuts -- often the biggest item in the category of cost synergies -- can be a key part of the process.

What also sometimes goes without saying, but shouldn't, is that it's a big responsibility to make or influence decisions that affect so many lives. Line managers, integration leaders and HR specialists are the ones likely to be most involved in specifics about organizational design and who stays or goes, with strategists and negotiators playing a secondary role. But as with nearly everything else in the team sport of corporate dealmaking, it's all of a piece if you're doing it right.

Most people who have been in M&A for a while can think of times when a team didn't handle the responsibility as well as it could have. The problem isn't necessarily a lack of compassion; sometimes it's more a lack of sleep, or information, or planning. Big mergers involve thousands upon thousands of decisions, and even under ideal conditions, some of them will redound to the unnecessary detriment of somebody, somewhere.

How to minimize the mistakes? With tools and processes, of course. The best-practices templates here are pragmatic and reassuring. Communicate, they remind us. Move swiftly and dispel uncertainty. Tell people where they stand. And remember that what you're really dealing with is human capital, an oddly (if usefully) detached way of thinking about people that also contains a handy nugget of optimism. Not only is talent valuable, it can also be managed and structured.

Social engineering may be frowned upon when the public sector tries it, but it turns out to be pretty popular at some large companies, at least at merger time. If you're combining two large organizations, specialists in human capital management will help you figure out what kind of culture you need, which potential leaders will help create it and which won't, and how to keep the talent pipeline flowing.

And though it can sound a little grandiose, it's better than trying to operate without a map or compass. It also sits squarely on the underlying economic premise for mergers and acquisitions. Deals are a way of catalyzing desirable or necessary change -- of directing resources, and people, toward more productive purposes. Build better companies, and you'll increase jobs in the long run.

Like other Big Pharmas, Pfizer was laying off employees and streamlining its underproductive R&D operations well before CEO Jeff Kindler and Wyeth CEO Bernard Poussot announced their deal. The new, decentralized setup is meant to tie the work more directly into the efforts of the business units, with subgroups for pharmaceuticals, biologics and vaccines. The result, according to Kindler, should be a much more effective integration than Pfizer managed in its last big deal, the $57 billion merger with Pharmacia Corp. in 2003. Ultimately, that should mean more new medicines at less cost.

It may be that Pfizer really has changed sufficiently since Kindler took over in 2006 for it all to be worthwhile this time. On the other hand, maybe the pharma CEOs vowing to refrain from giant mergers are the ones who have it right. Perhaps those laid-off chemists could have had a few more years to work on their career transitions.

With all our sophistication, it's still not so easy to say. Which is why one of the most valuable things a corporate dealmaker can bring to an exercise like this -- on a par with the analytical skills, drive and diplomatic talents prized in the craft -- is simply a little well-informed humility.