Histamine in serum and arterial tissue contributes to the pathogenesis of atherosclerosis and the formation of coronary artery vasospasm. As the effect of histamine at a given site will be mediated by its specific receptors, we investigated by in situ hybridization and Northern blot analysis the expression and localization of human histamine H1 receptor mRNA in the arterial wall and in cultured human aortic intimal smooth muscle cells (SMC) and immortalized SMC (ISS10) and endothelial cells (SE1). In situ hybridization showed that SMC and endothelial cells expressed H1 receptor mRNA in vivo and that the expression was increased in SMC in the thickened intima of atherosclerotic foci in both the aorta and coronary artery. By Northern blot analysis, we also detected histamine H1 receptor mRNA in cultured SMC, ISS10, and SE1 and found that platelet-derived growth factor stimulated SMC to increase their expression of the mRNA in vitro. These results suggest that up-regulation of histamine H1 receptor expression by platelet-derived growth factor plays an important role in the initiation and progression of cardiovascular diseases.