The calcium antagonists verapamil, D600, prenylamine, diltiazem and perhexiline inhibit chemotaxis and (stimulated) locomotion by rabbit polymorphonuclear leukocytes (PMN's). Inhibition occurs at relatively high concentrations (5.10(-5)-10(-3) M). Inhibition was most pronounced in the absence of extracellular Ca2+. In the presence of extracellular Ca2+ there was also inhibition of chemotaxis, but to a lesser degree than in the absence of Ca2+, thus extracellular Ca2+ partly reverses the inhibition of chemotaxis by calcium antagonists. The results suggest that the mechanism of action of these drugs in PMN chemotaxis differs from that in smooth muscle cell contraction, where much lower concentrations of these drugs are active. The data obtained suggest that calcium antagonists inhibit PMN chemotaxis and locomotion by interference with a Ca2+-dependent intracellular target.