The effect of metal salts, three nickel and one non-nickel (manganese chloride), was examined on the ability to influence mitogen stimulated normal human blood lymphocytes by means of short term in vitro culture and a tritiated thymidine incorporation test. Purified lymphocytes were incubated for one hour with tissue culture medium containing either one of the nickel salts tested (nickel subsulfide, nickel sulfate or nickel acetate) or manganese chloride. Separate portions of cells were incubated in the metal salt mixtures containing both, nickel and manganese salts. All metal salts were used in predetermined subtoxic concentrations. Two mitogens, phytohemagglutinin (PHA) and concanavalin A (Con A), were used as lymphocyte stimulatory agents. Cells were cultured for 72 hrs. It was found that following incubation with nickel salts, mitogen dependent lymphocyte stimulation was inhibited proportionally to the metal salt concentration. This blocking effect on tritiated thymidine incorporation was stronger for readily soluble nickel salts i.e. sulfate and acetate than for almost insoluble nickel subsulfide with either mitogen used. Manganese chloride used as a single salt resulted in a dose-dependent increase of lymphocyte stimulation as compared to the mitogen stimulated cells without preincubation with either metal (control samples). Cells preincubated with nickel salt-manganese chloride mixtures exhibited an increase of thymidine incorporation but below values for control cells.