The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p less than 0.05), ACTH (by 85%, p less than 0.05), AVP (by 89%, p less than 0.05), and ANH (by 36%, p less than 0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p less than 0.05). Cortisol did not change significantly. Infusion of 1 pmol.kg-1.min-1 of angiotensin II produced an elevation of aldosterone (by 186%, p less than 0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.