The ductus deferens smooth muscle tumor cell line (DDT1MF-2) expresses c-sis protooncogene mRNA transcripts which encode at least one subunit of the potent mitogenic agent, platelet derived growth factor (PDGF). These cells also synthesize and secrete a protein which is immunologically identical to this growth factor. Therefore, PDGF is implicated in the autocrine regulation of DDT1MF-2 cell proliferation. While androgens also stimulate proliferation and induce an augmentation in androgen receptor levels in DDT1MF-2 cells, glucocorticoids inhibit both events and arrest cells in the G1 phase of the cell cycle. Addition of PDGF overcomes the glucocorticoid cell cycle arrest, but does not diminish the suppressive action on androgen receptor concentration. These findings are consistent with a mechanism by which glucocorticoids regulate DDT1MF-2 cell proliferation through modulation of PDGF expression which is independent of the glucocorticoid effects on androgen receptor concentrations.