Atherosclerosis is characterised by unusual growth of vascular smooth muscle cells (VSMCs) in the intima. We examined the effects of histamine on human VSMCs and the VSMC-derived cell line, ISS10. Histamine enhanced phosphoinositide hydrolysis, increased cytoplasmic Ca2+ level and stimulated the transcription of c-fos protooncogene, which resulted in DNA synthesis and the enhancement of proMMP-1 expression. These results indicate that histamine may play some roles in the pathological process of atherosclerosis and raise the possibility that mast cells migrating into the atherosclerotic foci are involved in the process of atherosclerogenesis.