C-terminally truncated fragments of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) were tested for their ability to stimulate amylase secretion from pancreatic acinar cells and relax precontracted mesenteric arteries. h-alpha-CGRP, h-alpha-CGRP (1-36), h-alpha-CGRP (1-35), and h-alpha-CGRP (1-34) were made by Merrifield's solid-phase peptide synthesis methodology. Peptides were purified by gel filtration, cation-exchange chromatography, and semipreparative reversed-phase high-performance liquid chromatography. The products were characterized by amino acid analysis, mass spectrometry, and tryptic digestion. h-alpha-CGRP stimulated amylase secretion from dispersed guinea pig pancreatic acini in a biphasic concentration-dependent manner. The initial increase in amylase secretion reached 8% of total cellular amylase content with an ED50 value of 7.7 nM, and the second increase reached 11% of total cellular amylase content at a concentration of h-alpha-CGRP of 10(-4)M. h-alpha-CGRP (1-36) caused a small, significant increase in amylase release. C-terminally truncated fragments h-alpha-CGRP (1-35) and h-alpha-CGRP (1-34) did not increase amylase release at concentrations < 10(-5) M. At concentrations > 10(-5) M the fragments h-alpha-CGRP (1-35) and h-alpha-CGRP (1-34) caused a smaller increase in amylase release than that caused by h-alpha-CGRP whereas h-alpha-CGRP (1-36) caused the same increase. h-alpha-CGRP caused a concentration-dependent relaxation of rat mesenteric artery, precontracted with prostaglandin F2 alpha, with an EC50 of 2.9 nM and a maximal relaxation that was 60% of the prostaglandin F2 alpha-induced tone. h-alpha-CGRP (1-35) also relaxed the mesenteric artery in a concentration-dependent manner with a maximum response that was 40% of the prostaglandin F2 alpha-induced tone. The remaining fragments did not relax rat mesenteric arteries. Additionally, h-alpha-CGRP (1-36) and h-alpha-CGRP (1-34) did not block h-alpha-CGRP-induced relaxation of the mesenteric artery. An intact C-terminus is required for h-alpha-CGRP to cause potent biological effects in pancreatic acini and mesenteric artery. The different effects of h-alpha-CGRP (1-35) in mesenteric artery compared with those in pancreatic acini suggest that the CGRP receptors in these two tissues may be different.