The effect of histamine on T-cell colony formation was studied in human peripheral blood mononuclear cells. Histamine inhibited dose-dependently (10(-4)-10(-6) M) the colony formation of PHA-stimulated T-cells. The inhibition was similar in normal controls and rheumatoid arthritis (RA) patients in spite of the fact that in RA the colony formation was significantly lower than in the normal controls. No increase of colony formation was observed at low concentrations (less than 10(-7) M). Impromidine was less effective than histamine, and pyridylethylamine (PEA) was inactive. Cimetidine counteracted the effect of histamine while chlorpheniramine did not. The results show that colony formation may be inhibited through H2-receptors. This action may be of importance in cellular interactions in tissues with high local histamine concentrations.