Addition of increasing amounts of interleukin-4 (IL-4) to large granular lymphocytes (LGL) had a selective downregulative effect on the interleukin-2 beta-chain (p70) receptor expression. A 40% inhibition of the p70 expression compared to untreated cells was already observed after a 24-h incubation with IL-4. This decrease in p70 receptor expression had a marked suppressive effect on their proliferative response to IL-2. In addition, LGL cultured in the presence of both IL-2 and IL-4 substantially decreased the cytotoxic activity against the erythroleukemia cell line K562. Our data therefore indicate an important regulative role for IL-4 on the LAK-generation.