Gastric function was evaluated in conscious rhesus monkeys after an i.v. infusion of saline (0.11 ml/min) or leukotriene D4 (LTD4) (0.1 or 0.2 microgram/kg/min), a s.c. injection of nordihydroguaiaretic acid (4,4'-(2,3-dimethyl-1,4-butanediyl)-bis[1,2-benzenediol]) (NDGA), a nonspecific lipoxygenase inhibitor, or an intragastric bolus of (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl] methane sulfonamide) (Wy-48,252), a LTD4 receptor antagonist. Using a technesium diethylenetriamine-pentaacetic acid dilution technique, gastric emptying and secretion were determined in response to an 80-ml load of water. At the end of some studies, the animals were gastroscoped to obtain biopsies for histological evaluation. There were no differences in the microscopic appearance of the mucosa among the various groups. A continuous infusion of LTD4 significantly inhibited hydrogen and sodium ion secretion at doses that had no effect on systemic blood pressure or heart rate. In contrast, NDGA and Wy-48,252 had no effect on unstimulated (basal) fluid or ion secretion. Gastric emptying after the water load was unaltered by LTD4, but high doses of NDGA or Wy-48,252 decreased gastric emptying during the first 10 min. Thus, LTD4 does not appear to play a major role in gastric emptying or secretion in response to a water load, but may contribute to the changes in gastric function in response to potential gastric irritants.