Zinc (Zn) and selenium (Se) exert regulatory activities on immune functions, while cadmium (Cd) is an immunotoxic agent. The object of this study was to detect effects of 10(-4), 10(-5), and 10(-6) M Cd sulphate, Zn sulphate, and sodium selenite, and their combinations on human peripheral blood mononuclear cell (PBMC) proliferation and IFN-gamma and TNF-alpha production. Only 10(-5) M Zn sulphate significantly enhanced spontaneous PBMC proliferation, which was unaffected by the other salts. At 10(-4) and 10(-5) M, Cd sulphate exerted a dose-response inhibitory action on phytohemagglutinin- (PHA-) stimulated PBMC proliferation and cytokine release, while 10(-4) M and 10(-5) M Zn sulphate and 10(-5) M sodium selenite induced a stimulatory effect on both proliferation and cytokine release; 10(-4) M sodium selenite enhanced only the PBMC proliferation; at 10(-6) M, none of the salts changed the PHA-stimulated immune activity. Moreover, 10(-4) and 10(-5) M Zn and 10(-5) M Se strongly upregulated IFN-gamma (a Th1 cytokine) release, even in presence of 10(-5) M Cd, and reduced the inhibitory effects of Cd on PBMC proliferation and TNF-alpha release. This study confirms that Zn and Se both strongly enhance cytokine release induced by mitogenic stimulation, showing also that Zn acts with a broader range of concentrations than Se. This suggests that dietary excess of Se may not have beneficial effects.