Approximately one half of the aldosterone-producing adenomas (APA) removed from patients with primary aldosteronism in the Hypertension Unit at Greenslopes Hospital belong to a subgroup in which aldosterone levels are responsive to the renin-angiotensin system (angiotensin-responsive APA; AII-R-APA), unlike classical APAs in which aldosterone is unresponsive (AII-U-APA). Renin mRNA levels in AII-R-APA were elevated when compared with those in AII-U-APA or normal adrenal cortices. Renin mRNA levels in some adrenal cortices surrounding AII-R-APA (but never in AII-U-APA) were raised, suggesting that a genetic defect is not confined to the tumor. Renin gene RFLP analysis in peripheral blood DNA revealed a significant difference in allelic frequencies between patients with AII-R-APA and AII-U-APA, suggesting an association between an alteration in the renin gene and aldosterone responsiveness to the renin-angiotensin system in patients with APAs.