The effects of atropine, proglumide, and somatostatin analogue (SMS 201-995) on bombesin-induced gallbladder contraction and plasma cholecystokinin (CCK) secretion were investigated in healthy volunteers. The gallbladder size was measured by real-time ultrasonography and the plasma CCK levels by radioimmunoassay. Bombesin (5 micrograms/30 min infusion) induced gallbladder contractions that reduced the gallbladder area to 36.6 +/- 2.1% of the original area 45 min after bombesin infusion, and caused a significant increase of plasma CCK from a basal level of 10.3 +/- 1.8 pg/ml to a peak level of 42.9 +/- 8.9 pg/ml (p less than 0.01) at 20 min. Atropine (500 micrograms, im) inhibited significantly (p less than 0.01) the gallbladder contraction (maximum contractile rate, 78.7 +/- 6.4%) in response to bombesin without any change of plasma CCK secretion, whereas proglumide (800 mg/day for 3 days, per os) decreased slightly but not significantly the gallbladder contraction, and had no effect on plasma CCK secretion. On the other hand, SMS 201-995 (50 micrograms, sc) almost completely inhibited both bombesin-induced CCK secretion and gallbladder contraction (maximum contractile rate, 93.6 +/- 6.2%). These findings suggest that atropine inhibits bombesin-induced gallbladder contraction, not via suppression of CCK release, but probably by inhibiting cholinergic mechanisms, whereas somatostatin inhibits gallbladder contraction, at least in part, by the suppression of bombesin-stimulated CCK secretion.