Orthovanadate and genistein were employed to determine the possible role of tyrosine kinase in the prolactin stimulation of cell division in Nb2 node lymphoma cells. Orthovanadate (0.1-0.25 microM), an inhibitor of specific phosphatases, was found to stimulate cell division as well as potentiate the mitogenic effect of prolactin on Nb2 cells when prolactin was employed at a less than maximum stimulatory concentration. Genistein, an inhibitor of tyrosine kinase, was found to inhibit the prolactin stimulation of cell division. Since prolactin was shown in earlier studies to stimulate the phosphorylation of tyrosyl residues in specific Nb2 cell proteins, these results suggest that the signal transduction pathway for the prolactin stimulation of cell division in the Nb2 node lymphoma cells likely involves the participation of tyrosine kinase(s).