Dopamine is taken up by platelets by an energy and temperature dependent process that does not involve a known dopamine receptor. Whilst dopamine uptake by platelets has been shown to be altered in several disease states, little is known about factors controlling dopamine uptake by platelets which could cause such changes. As phorbol esters have been shown to affect dopamine functions in other tissues we examined the effect of phorbol esters on dopamine uptake by human platelets. Phorbol 12,13-dibutyrate increased [3H]-dopamine uptake by platelets in a dose dependent manner. Similarly, phorbol 12,13-didecanoate increased [3H-dopamine uptake by platelets but 4α phorbol 12,13-didecanoate, which does not affect protein kinase, did not. Staurosporin, a protein kinase inhibitor, reversed the effect of phorbol 12,13-dibutyrate. These data suggest protein kinases can modulate dopamine uptake by platelets.