Inhibiting protein kinase C (PKC) activity abrogated interleukin 2 (IL2) production by mitogen-stimulated human T lymphocytes. This effect was due partially to a 50% decrease in IL2 gene expression. However, when PKC inhibitors were added after IL2 gene transcription had already proceeded for 3-4 h, the IL2 in the culture supernatants was still reduced by 30-80%, and intracellular IL2 was increased by up to 50%. The inhibition of PKC affected the expression of IL2 receptors by these cells differently; it had little effect on gene expression or on the membrane-bound form of the receptor, but it decreased soluble receptors in the supernatants by 50-80%. These data indicate that in addition to its previously defined role in gene expression, PKC can also regulate extracellular secretion of proteins critical for T cell proliferation.