This week, during a meeting with analysts and investors, the company's new chief executive, Jeffrey B. Kindler, announced that Pfizer was going to do some serious retrenching. For starters, it would lay off 7,800 people. Along with a previously announced reduction of 2,200 sales representatives, that meant Pfizer was going to cut 10,000 jobs, about 10 percent of its work force.

He also announced that Pfizer would close some of its manufacturing and research facilities and reconfigure its research capabilities. But most important, Mr. Kindler did something his predecessor, Hank McKinnell, who was shown the door last summer well ahead of his scheduled retirement (and handed an obscene exit package), had never been able to do.

Implicitly at least, Mr. Kindler acknowledged that Pfizer had hit the wall. Despite the nearly $15 billion it made last year it; despite the fact that it still has the best-selling drug in the world, Lipitor, which generates around $13 billion in annual revenue - its reliable business model had begun to break down. Mr. Kindler's essential message to the investment community was that Pfizer was going to try to do the single hardest thing any big company can try, and that is to change.

We in the newspaper business tend to obsess about the wrenching transformation taking place in the media industry. It is easy enough to see. We look at other industries, like the domestic auto business, and we can see that its way of doing business isn't working anymore either.

It is a little harder to see that with Big Pharma, which is still rolling in profits. But the pharmaceutical business is, indeed, changing. "I think of the environment as a huge screw that is slowly turning," said Steve Scala, the health care analyst with Cowen & Company. "You can't see it turning if you are in the middle of it, but if you walk away for a while and then come back, you notice how much it's turned." For Pfizer, the very tactics that made it so successful for so long are precisely the ones that have now caused the company to stumble.

Mr. Kindler has noticed that the screw is turning. Whether he can actually do anything about it, retrenchment or not, is another question entirely. THE modern Pfizer was built on blockbusters, which is what the industry calls medicines that generate $1 billion or more in annual revenue. That isn't exactly a news flash: There was Viagra, which it brought to market in the late 1990s and turned into a $1.6 billion drug, and its high-blood-pressure medication Norvasc ($4.8 billion in sales last year). And Lipitor, which, despite competing with a handful of other cholesterol-lowering drugs, is by far the dominant drug in its class.

In the 1980s and 1990s, all the big pharmaceutical companies aimed for blockbusters, of course. But no company was better at it, and no company believed more profoundly in the supremacy of the blockbuster model. Pfizer was in the forefront of the mass marketing of drugs, and of getting its sales force in front of doctors to persuade them to use Pfizer's products instead of a competitor's. And if its research labs weren't exactly prolific - Pfizer hasn't developed a blockbuster on its own since Viagra - it still managed to produce a steady stream of blockbusters by buying up other companies and acquiring their potential blockbusters. Mr. McKinnell used to say that there were plenty of blockbusters out there - Pfizer's job was to go out and find them.