Nitrendipine, nifedipine and verapamil inhibit the in vitro formation of irreversibly sickled cells. Using a method of forming both dehydrated cells and irreversibly sickled cells in vitro by repeated cycles of sickling and unsickling, the effects of several drugs in inhibiting the formation of these cells were studied. Drugs known as Ca2+ channel antagonists, such as nitrendipine, nifedipine and verapamil were found to inhibit these reactions. Other types of calcium channel blockers, such as lanthanum and zinc, did not inhibit the formation of these cells. The potency of drugs to inhibit irreversibly sickled cell formation was related to the potency of inhibition of calmodulin-activated phosphodiesterase.