The role of capsaicin-sensitive pathways and CGRP in postoperative gastric ileus was investigated. Abdominal surgery was performed under enflurane anesthesia, and 5 min later, the 20-min rate of gastric emptying was measured by the phenol red method in conscious rats. Surgery inhibited gastric emptying by 76-83% compared with rats receiving anesthesia alone. Capsaicin on the celiac/mesenteric ganglia (10-21 days before) reduced gastric ileus by 33 +/- 8%, whereas perivagal capsaicin had no effect. The IV CGRP-induced inhibition of gastric emptying was completely reversed by the CGRP antagonist, CGRP(8-37) (30 mug, IV); CGRP(8-37) (15, 30, or 60 mug) or CGRP monoclonal antibody #4901 (2 mg protein) decreased the inhibition of gastric emptying by 11 +/- 7%, 51 +/- 13%, 47 +/- 3%, and 45 +/- 17%, respectively. These results indicate that CGRP and splanchnic capsaicin-sensitive afferents are involved in mediating part of the gastric ileus observed immediately after abdominal surgery.