We have studied activation of mitogen-activated protein kinase (MAP kinase) and [3H]-thymidine uptake as a marker for cellular proliferation in a proximal tubular cell line of the American Opossum kidney (OK cells). Adrenaline, serotonin, epidermal growth factor and insulin all stimulated MAP kinase and [3H]-thymidine uptake. This stimulation of cellular proliferation was markedly reduced by an inhibitor of the MAP kinase pathway, PD 98059. Epidermal growth factor stimulated MAP kinase activity more effectively than the other agonists, but all four had similar effects on OK cellular proliferation. These data indicate that amine neurotransmitters may be of similar importance for tubular regeneration as classical growth factors.