Cocaine, used intravenously, increases the risk of infections, but its effects on neutrophil phagocytosis have not been examined in vitro. Human neutrophils were suspended in cocaine hydrochloride 0, 1, 10, 50, 100 or 200 microg/ml in Hank's balanced salt solution to which was added a phagocytic meal of killed Saccharomyces cerevisiae stained with the pH indicator dye bromcresol purple. Yeast per phagocytosing neutrophil and the percent neutrophils phagocytosing yeast were reduced in neutrophils treated with cocaine 100 and 200 microg/ml (P < 0.05). When examined for percent of yeast phagocytosed after 10 minutes, neutrophils treated with cocaine 1-200 microg/ml demonstrated a decrease (P < 0.05). However, at 60 minutes only neutrophils treated with cocaine 50 and 100 microg/ml still showed a decrease in percent of yeast phagocytosed. Phagolysosomal acidification was impaired in neutrophils treated with 50, 100 and 200 microg/ml cocaine. Thus, cocaine inhibits neutrophil phagocytosis and phagolysosomal acidification in vitro, offering a reason for cocaine users/abusers to have impaired host defense and to be potentially at higher risk for infections.