The human calcitonin gene-related peptides I and II (or alpha and beta) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p less than 0.01), and the heart rate (p less than 0.05), and plasma renin activity and aldosterone secretion than human CGRP II (p less than 0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and II on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides.