The effects of endothelin-1 on DNA synthesis and expression of genes related to cell proliferation in rat vascular smooth muscle cells (VSMC) were investigated by 3H-TdR incorporation and Northern blot analysis. The results suggest that 3H-TdR uptake increased at 12 h after stimulation with endothelin-1, with reaching a peak at 24 h.Endothelin-1 induced rapidly and transiently the expression of the proto-oncogenes c-fos and c-jun,the activity of their expression peaked at 30 min after stimulation, and rapidly declined there after. The expression of the p34cdc2 kinase gene augmented at 12 h after endothelin-1 stimulation and continuously expressed at relatively high levels until 24 h. These data indicate that endothelin-1 stimulates DNA synthesis of VSMC by inducing the transcription of genes related to cell proliferation.