As an approach to study the mechanisms regulating the surface expression of CD5 antigen on T cells, the effects of agents that activate different lymphocyte functions were examined. Active tumour promoter agents (TPA), such as phorbol ester analogues [phorbol 12-myristate 13-acetate (PMA), phorbol 12, 13-dibutyrate (PBu2)] and mezerein, were able to increase the expression of CD5 on the cell surface of all T-cell lines), as deduced from immunofluorescence and immunoprecipitation analysis. The TPA-induced CD5 up-regulation occurred in a dose-and time-dependent manner and was dependent on protein and RNA synthesis. From the other stimuli tested, the T-cell mitogens [phytohaemagglutinin (PHA) and concanavalin A (Con A)], as well as monoclonal antibodies (mAb) against the CD3 complex, also increased CD5 expression, although to a lesser degree. In all cases the increments were shown to be dependent on protein kinase C (PKC), as evidenced by their inhibition with staurosporine, a potent inhibitor of PKC activation. These data suggest that CD5 up-regulation on T cells can be a physiological event that depends on PKC activation.