Effects of interferon (IFN) on PHA-induced interleukin 2 (IL-2) production by human peripheral mononuclear cells were studied comparatively with natural human IFN-alpha, IFN-beta and IFN-gamma, using an equivalent unit of their antiviral activity ranging from 10 to 1000 IU/ml. IL-2 activity was assessed in cultures with or without IFN by a standard bioassay using murine CTLL-2 cells. PHA-induced production of IL-2 in cultures of peripheral mononuclear cells was unaltered or slightly suppressed by the simultaneous presence of IFN-alpha and IFN-beta. The effect was the same, whether or not indomethacin was present in the cultures. In contrast, the addition of IFN-gamma to the PHA-stimulated cultures markedly enhanced IL-2 production, while IFN-gamma per se had no effect on IL-2 production in the absence of PHA. The enhancement of IL-2 production due to IFN-gamma was more marked in cultures which did not include indomethacin than in cultures which contained indomethacin (1 x 10(-6) M).