The drug pyrithioxine strongly stimulated in vitro migration by rabbit peritoneal neutrophils. The stimulating effect appeared to be chemotactic rather than chemokinetic. Though the drug did not induce exocytosis by itself, it stimulated fMet-Leu-Phe-induced exocytosis. The effect on exocytosis induced by other activators was not statistically significant. No stimulating effect of pyrithioxine on superoxide production was observed, either in the absence or in the presence of activators. For a maximal stimulating effect on migration and exocytosis the presence of extracellular Ca2+ was required. Pyrithioxine caused an increase of cGMP level in neutrophils. The hypothesis is presented that the differential activation of neutrophil functions by pyrithioxine is mediated by cGMP, and that cGMP has a differential importance for the neutrophil functions studied.