In the present study we have evaluated the effect of calcitonin gene-related peptide (CGRP) on cyclic AMP levels in intact mouse kidneys. We have used an in vivo bioassay based on microwave irradiation as a means of rapid tissue fixation, followed by the determination of cyclic AMP concentration using a protein binding assay. CGRP was found to cause a dose-dependent elevation of renal cyclic AMP levels, and despite being slightly less potent than calcitonin (CT), the action of CGRP was significantly more prolonged. The extended time course of action of CGRP is in sharp contrast to its known effect on bone cyclic AMP levels and could be of physiological relevance. CGRP may act on a receptor different from that of CT to produce distinct functional effects.