The present study was undertaken to determine whether atropine inhibits the plasma cholecystokinin (CCK) response to intraduodenal fat. Plasma CCK concentrations were measured by radioimmunoassay using two sequence-specific antibodies. Antibody 1703 bound to all COOH-terminal CCK peptides containing at least 14 amino acid residues, while antibody T204 was specific for the sulphated tyrosine region of CCK. Intraduodenal instillation of 60 ml corn oil in 6 normal subjects induced significant increases in plasma CCK. Intravenous administration of atropine (0.015 mg/kg as bolus followed by 0.005 mg/kg · h over 3 h) resulted in significant inhibition of plasma CCK concentrations at 10, 20 and 30 min (antibody 1703) and at 20 and 30 min (antibody T204) after instillation of fat. However, the peak increments in plasma CCK during atropine (8.6 ± 1.9 pmol/l, antibody 1703; 5.4 ± 1.1 pmol/l, antibody T204) were not different from those found without atropine (6.3 ± 0.8 pmol/l, antibody 1703; 3.9 ± 0.9 pmol/l, antibody T204). Similarly, the integrated plasma CCK secretion after intraduodenal fat was not significantly different when measured during atropine (461 ± 119 pmol/l·3 h, antibody 1703; 269 ± 97 pmol/l·3 h, antibody T204) and without atropine (428 ± 62 pmol/l·3 h, antibody 1703; 188 ± 66 pmol/l·3 h).It is concluded that administration of atropine delays but does not inhibit the CCK response to intraduodenal cor