A noncholinergic nicotine receptor on human phagocytic leukocytes has been characterized using the binding of 3H-(d,1)-nicotine. The average affinity +/- standard deviation of (d,1)-nicotine for the receptor on neutrophils is 36 +/- 18 nM (n = 6). The binding is saturable with an average of 8.7 x 10(4) sites per neutrophil. Monocytes and to a lesser extent lymphocytes but not erythrocytes also display specific binding. Bound nicotine is dissociable from the receptor and is not metabolized. Only close structural analogs of nicotine bind to the receptor, which is stereoselective for the (d)-isomer. The receptor can be occupied by (1)-nicotine at concentrations present in the blood of smokers. It is suggested that some of the adverse effects of smoking on leukocyte functions may be mediated by a specific nicotine receptor.