1. The 37 amino acid human calcitonin gene-related peptide (CGRP), was injected intra-arterially into the isolated, blood perfused spleen of the dog. 2. The only vascular response observed to CGRP, once threshold had been reached (10-20 fmol), was a dose-dependent splenic arterial vasodilatation. 3. The mean intra-arterial bolus dose of CGRP to reduce the splenic arterial vascular resistance by 50% of maximum response was 0.52 +/- 0.12 pmol. This value was significantly lower than the ED50 for the non-selective beta-adrenoceptor agonist isoprenaline (P less than 0.01) in the same experiments. CGRP is the most potent splenic vasodilator yet tested. 4. The mean maximum vasodilator response to CGRP was significantly less (P less than 0.001) than that achieved with isoprenaline. 5. The time course of the splenic arterial vascular response to CGRP was substantially longer than that to isoprenaline. 6. The splenic vasodilator response to CGRP was not altered by the prior administration of the selective beta 2-adrenoceptor antagonist, ICI 118,551. 7. At all doses of CGRP that caused splenic vasodilatation there were substantial increases in spleen volume. The time course of the response and slope of the regression line suggested an active capsular relaxation component. 8. In view of its location within the spleen and high molar potency, CGRP may be considered as a potential factor in the local control of the circulation through the spleen.