We investigated the mechanism of suppressive effect of alveolar macrophages (AM) on autologous blood NK cell activity in healthy nonsmokers (NS) and smokers (S). A 50 percent additional concentration of AM both in NS and S inhibited NK cell activity significantly (p less than 0.05). The degree of inhibition was not different in NS and S. Effects of prostaglandins (PG) and oxygen radicals were studied separately on the NK cell activity in the presence of AM. Indomethacin, catalase, or thiourea did not reverse inhibition of NK cell activity, but superoxide dismutase (SOD) prevented this phenomenon. These results suggest that the inhibition of NK cell activity by AM may be caused by O2 release rather than PG, H2O2, and OH.