Calcitonin gene-related peptide (CGRP) and the selective antagonist properties of the peptide fragment of CGRP [CGRP (8-37)] have been the subjects of numerous investigations. These data represent the first demonstration of the hypothermic and antinociceptive effects of CGRP (8-37). Intrathecal injection of CGRP (8-37) in mice produced hypothermia which differed from that produced by CGRP in time course, duration of action and potency. CGRP and CGRP (8-37) did not alter blood flow. Thus, a direct vasodilatory action was not responsible for the acute hypothermic effects of the drugs. The combination of CGRP and CGRP (8-37) resulted in a decrease in body temperature which was no greater than that of either drug alone. We failed to observe any significant antinociceptive effect in the tail-flick assay after i.t. injection of CGRP (8-37), but dose-dependent antinociception was produced by CGRP (8-37) in the p-phenylquinone (PPQ) assay, with an ED50 value of 6.0 micrograms. However, CGRP (8-37) failed to block or enhance the antinociception produced by CGRP over a wide dose range. In addition to demonstrating an agonist-like effect for CGRP (8-37), these data also indicate that CGRP and CGRP (8-37) may not act through a common mechanism.