The circadian monitoring of intragastric pH and of the mutagenicity of 440 gastric juice samples collected hourly from 22 subjects provided evidence that, irrespective of diagnosis and treatment, a weak yet consistent increase in revertants can be detected in his- Salmonella typhimurium strains during the 3-4-h periods following each meal. The recorded mutagenic activity was not related to the histidine content of gastric juice, was due to thermostable components and was not significantly inhibited by administration of vitamin C. Various genetic mechanisms were involved, which were different from those consequent to the artificial supplementation of gastric juice with sodium nitrite. Treatment with a histamine H2-receptor antagonist (famotidine), either at dinner or at bedtime, was followed by a nocturnal plateau of mutagenicity. However, such effect was not due to mutagenicity of the drug or of its derivatives, but to the therapeutic rise in pH associated with its antisecretory activity.