Since bombesin is known to stimulate pancreatic enzyme secretion and gallbladder contraction, we have measured plasma cholecystokinin (CCK) concentrations during bombesin infusion using sequence-specific radioimmunoassays. Antibody 1703 binds to COOH terminal CCK peptides containing at least 14 amino acid residues, while antibody T204 is specific for the sulfated tyrosine region of CCK. In nine normal persons infusion of increasing doses of bombesin (2.4, 6, 18, and 60 pmol/kg X 20 min) induced dose-related integrated plasma CCK responses (58.5 +/- 9.7, 70.5 +/- 12.2, 79.5 +/- 11.1, and 101.4 +/- 15.4 pmol/L X 20 min [antibody 1703] and 50.4 +/- 11.9, 62.0 +/- 13.4, 74.7 +/- 9.2, and 116.1 +/- 11.3 pmol/L X 20 min [antibody T204]). Infusion of 60 pmol bombesin/kg X 20 min in eight patients with partial gastrectomy resulted in similar increases in plasma CCK (8.1 +/- 1.8 pmol/L, antibody 1703; 9.5 +/- 2.0 pmol/L, antibody T204) as in eight normal control subjects (6.5 +/- 0.9 pmol/L, antibody 1703; 8.8 +/- 1.0 pmol/L, antibody T204). During infusion of bombesin, plasma gastrin levels increased from 16.7 +/- 1.4 to 49.6 +/- 8.1 pmol/L (P less than 0.005) in the normal persons, while there was no significant change in plasma gastrin levels in gastrectomized patients. Bombesin did not significantly influence gastric acid secretion in three patients with partial gastrectomy studied. It is concluded that infusion of bombesin releases CCK in humans by a gastrin-independent mechanism.