Activation of T lymphocytes results in immediate biochemical changes including increases in intracellular calcium levels, activation of protein kinase C (PKC) and changes in tyrosine phosphorylation. In T cells recent studies have indicated that activation of the guanine nucleotide-binding proteins p21ras is mediated by PKC, which suggests that the p21ras proteins may regulate intracellular signalling events downstream of PKC. The p21ras proteins can be activated in T cells by signals generated by triggering of the T cell antigen receptor (TCR), the CD2 antigen and the interleukin 2 receptor. Experiments using a PKC pseudosubstrate inhibitor indicate that PKC does not mediate TCR-induced activation of p21ras. These results imply that an alternative signal transduction pathway not involving PKC can regulate the activity of p21ras proteins in T cells.