Objective:To establish the role of prostaglandin E2(PGE2) formed and released by monocytes and monocyte‐derived macrophages (MDM) in the reduced toxoplasmastatic activity of these cells.Design:Determination of PGE2levels in the serum of AIDS patients, the release of PGE2by monocytes and MDM from AIDS patients, the toxoplasmastatic activity of these cells and the effect of indomethacin, an inhibitor of PGE2synthesis, on this cell function.Setting:Laboratory of Cellular Immunology of the Department of Infectious Diseases, University Hospital, Leiden.Participants:Twenty‐six AIDS patients. Healthy blood donors served as controls.Results:The concentration of PGE2in the serum from AIDS patients was significantly higher compared with serum from controls. Non‐stimulated monocytes and lipopolysaccharide‐stimulated monocytes and MDM from AIDS patients released significantly more PGE2than corresponding cells from the controls. The proliferation ofToxoplasma gondiiin monocytes and MDM from AIDS patients was significantly higher than in the respective cells from controls. Preincubation of these cells with indomethacin resulted in a decreased proliferation ofT. gondiiin non‐activated monocytes and MDM and in interferon‐&ggr;‐activated MDM from AIDS patients. Preincubation of monocytes from healthy donors with PGE2resulted in a dose‐dependent increase ofToxoplasmaproliferation which confirms that PGE2can reduce the toxoplasmastatic activity of monocytes.Conclusion:PGE2is involved in the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients.AIDS 1995,9:441‐445