The effects of cadmium (Cd) in non-cytotoxic conditions on the nitric oxide (NO) production in peritoneal macrophages (pM) were studied. Peritoneal macrophages from Balb/c mice were incubated over 18 h with 5, 10, 20, or 25 microM Cd2+ (as CdCl2 21:2 H2O) in the culture medium. Concentrations of 20 microM Cd2+ and over had cytotoxic effects, measured by MTT assay. Cell viability with 10 microM Cd2+ in the medium was above 90% after 18 h of incubation, and above 80% after 72 h. At this same Cd2+ concentration, NO production increased from 6 to 18 h. At 24 h production decreased but was still above control levels. At 48 h production NO was near control levels, and continued to decrease until the end of the experiment (72 h). NO levels produced with Cd2+ concentrations of 5, 10 and 20 microM in the medium were above the control at 18 h. NO production and lipoperoxidation increased simultaneously after 18 h with 10 microM of Cd in the medium. Amounts of inducible nitric oxide synthase (iNOS) protein and iNOS activity also increased. At a concentration of 10 microM Cd has a biphasic effect on NO production over time.