Phorbol ester activates human lymphocyte proliferation as measured by [3H]thymidine incorporation and blast transformation. Phorbol ester and calcium ionophore A 23187 induce c-fos and c-myc expression in these cells as shown by the measure of the specific mRNA levels and of the c-fos nuclear protein amount. The combination of these two agents has a synergistic effect on c-fos but not on c-myc expression. Lymphocyte stimulation by phorbol ester for a short time induces c-fos and c-myc expression, but has no effect on [3H]thymidine incorporation. This result indicates that the induction of c-fos and c-myc expression is not sufficient to commit these cells to DNA synthesis.