Peripheral blood large granular lymphocytes (LGL) expressing Leu 11 (CD16) antigen with potent natural killer cytotoxicity inhibited soluble antigen-induced T-cell production of interleukin 2 (IL-2). Depletion of Leu 11-reactive cells from T-cells doubled IL-2 activity (P less than 0.05). Leu 11-enriched cells did not express high affinity IL-2 receptors nor did they deplete IL-2 activity from culture media. Upon addition in low ratios to Leu 11-depleted cells, Leu 11-enriched fractions increased antigen-induced IL-2 production three-fold (P less than 0.05), whereas at higher ratios IL-2 production was suppressed P less than 0.01. Additionally, adherent monocytes were increasingly accessory when added in graded numbers to Leu 11-depleted but not T-cell cultures. In the presence of small numbers (5%) of Leu 11-enriched cells, however, monocytes down-regulated IL-2 production of Leu 11-depleted cell cultures. Thus Leu 11-reactive lymphocytes have noncytotoxic functions and may play a major role in immunoregulation.