The cardiac renin-angiotensin system has been suggested to be involved in various pathological conditions, including hypertrophy and remodeling. However, direct evidence that renin synthesized in situ is really involved in the putative angiotensin II generation is still lacking because of the relatively low abundance of renin mRNA in cardiac tissues. We evaluated renin mRNA expression levels in the ventricles under various pathological conditions and found that renin gene expression was markedly increased in the ventricles of isoproterenol-treated rats. Renin mRNA expression levels in the ventricles of rats that had been injected with isoproterenol (150 mg/kg SC) were transiently and markedly increased to 6-, 90-, and 4-fold compared with control expression levels at 24, 72, and 120 hours, respectively, after isoproterenol administration, Immunohistochemical analysis revealed that some of the OX-42-positive macrophage/monocyte cells had a reninlike immunoreactivity. An in vitro experiment indicated that rat peritoneal macrophage/monocyte cells expressed renin mRNA in abundance. The present study confirmed that a subpopulation of macrophage/monocyte cells could express renin. Macrophage/monocyte cells may be a source of tissue renin in some pathological conditions.