1. The presence of Cd2+, Ni2+, Cu2+, Mn2+ and Co2+ (10(-4)-10(-6) M) caused a dose-dependent inhibition of DNA synthesis in phytohemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) from normal human donors. No inhibition of DNA synthesis was observed in the presence of Mg2+ and Al3+. 2. Spontaneous and PHA induced interleukin-1 (IL-1) was enhanced in the presence of Mn2+. 3. The release of interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R) was decreased by Cd2+, Cu2+ and Mn2+. 4. Spontaneous tumor necrosis factor-alpha (TNF-alpha) production was enhanced by Co2+ and Al3+, but decreased by Cd2+. 5. gamma-Interferon (gamma-IFN) production was decreased in the presence of Cd2+ and Cu2+ and increased in the presence of Al3+.