This study was undertaken to investigate the effect of erythromycin, a motilin agonist with prokinetic activity, on fasting gallbladder volume. To evaluate the mechanism of action of erythromycin on gallbladder motility, erythromycin (3.5 mg/kg.20 min, intravenously) was infused on three separate occasions: during cholinergic blockage with atropine (0.005 mg/kg.hr), during cholecystokinin receptor blockade with loxiglumide (10 mg/kg.hr) and during saline solution infusion (control). Atropine, loxiglumide and saline solution infusions were started 3 hr before administration of erythromycin and were continued for 3 hr thereafter. Gallbladder volumes (measured by ultrasonography), plasma cholecystokinin levels (radioimmunoassay) and plasma pancreatic polypeptide levels (radioimmunoassay) were determined at regular intervals for 6 hr in six healthy volunteers. During the 3-hr infusion before administration of erythromycin, both loxiglumide and atropine significantly increased gallbladder volumes--from 18 +/- 2 to 37 +/- 3 cm3 (p less than 0.05) and from 17 +/- 3 to 24 +/- 2 cm3 (p less than 0.05), respectively--whereas saline solution did not significantly affect gallbladder volume. During control saline solution infusion, erythromycin induced prolonged gallbladder contraction that was significant (p less than 0.05) between 60 and 180 min and reached a maximum of 45% +/- 8% at 150 min. Plasma cholecystokinin levels were not affected by erythromycin. Erythromycin induced a significant (p less than 0.05) increase in plasma pancreatic polypeptide levels, from 12 +/- 1 pmol/L to 34 +/- 3 pmol/L. Loxiglumide did not prevent the erythromycin-induced reduction in gallbladder volume. Atropine markedly reduced the effect of erythromycin, causing slight but significant (p less than 0.05) gallbladder volume reductions (18% +/- 4%) between 150 and 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)