The effect of three benzodiazepine compounds, diazepam, flunitrazepam, and clorazepate, on oxidative activity of human polymorphonuclear leukocyte (PMN) was investigated. The oxidative activity of zymosan-stimulated PMN in the presence of three concentrations (10, 20, and 40 μg/ml) of these compounds was measured polarographically. In addition, zymosan-stimulated nitroblue tetrazolium (NBT) reduction was measured in the presence of various concentrations of flunitrazepam. All three compounds inhibited oxygen consumption of the PMN. The extent of inhibition was linear with respect to log-concentrations; oxygen consumption was reduced 50% for concentrations of diazepam, flunitrazepam, and clorazepate of 13 μg/ml, 56 μg/ml, and 285 μg/ml, respectively. In addition 30% and 100% inhibition of NBT reduction by flunitrazepam were observed at respective concentrations of 10 μg/ml and 60 μg/ml. The clinical relevance of these findings remains to be determined.