The influence of omeprazole on the antiulcer effects of histamine, methacholine and pentagastrin on ethanol-induced gastric ulceration was studied. Histamine 5 mg/kg, methacholine 500 micrograms/kg or pentagastrin 100 micrograms/kg pretreatment s.c. markedly reduced ethanol (50%, 10 ml/kg p.o.)-induced gastric ulceration in pylorus-ligated conscious rats, but significantly elevated the gastric secretory volume and acid output. Omeprazole pretreatment 50 mg/kg s.c. reduced gastric secretion and abolished the ulcer-protecting effects of the three secretagogues. The same doses of histamine, methacholine or pentagastrin did not significantly alter the gastric secretory volume but increased the total acid output of ex-vivo stomach chamber preparations in anaesthetised animals. Histamine worsened ethanol-evoked ulceration whereas methacholine and pentagastrin had no effect on the lesions. Omeprazole pretreatment did not prevent ulcer aggravation by histamine. It is concluded that the antiulcer effects of the three secretagogues in conscious animals are probably due to the increased secretory volume which lessens the ulcerogenic action of ethanol by its dilution. Omeprazole reduces the secretory volume and thus prevents the antiulcer effect of these secretagogues. The findings with histamine and omeprazole in the ex-vivo stomach experiments support the suggestion that it is unlikely that increased gastric acid secretion affects the ulcerogenicity of ethanol in rat stomach.