The acquired immune deficiency syndrome (AIRS) is characterized by multiple opportunistic infections which are normally killed by phagocytic cells of the reticuloendothelial system (RES). We have prospectively analysed in vivo RES function by measureing Fc receptor clearance and C3b-receptor clearance in AIDS patients and patients at risk for AIDS. In vivo RES clearance defects. A total of 63 patients have been studies, including 22 AIDS patients, 9 patients with AIDS-related complex, 13 healthy homosexual men, 15 healthy heterosexuals and 4 heterosexuals with mycobacterial disease but without AIDS. Eleven of fifteen AIDS patients and 2 of 9 with AIDS-related complex had prolonged Fc specific clearance rates compared to controls. In contrast, patients with mycobacterial infection but without AIDS had significantly more rapid clearance rates reflective of activated macrophage function. Similarly, C3b clearance rates were markedly abnormal in 7 AIDS patients compared to controls. Patients with AIDS had a relatively large initial clearance of C3b labeled cells, but unlike controls, they had a relatively large release of cells back in circulation. These defects of both Fc and C3b clearance rates suggest a marked phagocytic defect of the RES. In vitro phagocytic defects. In order to measure the degree of phagocytic defect, we investigated antibody directed cell mediated cytoxicity (ADCC) of peripheral blood mononuclear cells of patients with AIDS against chicken red blood cells (CRBC). Compared to healthy controls, a marked decrease in ADCC-CRBC activity was observed in mononuclear cells from AIDS patients. No suppression in ADCC activity was seen when mononuclear cells from healthy subjects were assayed using media containing 10% sera from AIDS patients. The significance of this project is in the identification of a marked phagocytic defect both in vivo and in vitro in patients with AIDS. Further studies will examine the severity and characterization of the phagocytic defect.