The mutagenic activity of gastric juice has been assessed using bacterial tester strains that undergo reverse mutation (Salmonella typhimurium:his(-)----his(+)). Free histidine, a known source of inaccuracy in this mutation test system, was detected in 42 of 73 juice samples (concentration range 3.5-992.4 micrograms/ml); high histidine concentrations were significantly correlated with hypochlorhydria. The effect of histidine was controlled by using a pre-incubation modification of the Salmonella fluctuation test in which juice samples and their corresponding control cultures containing equivalent amounts of histidine were incubated with the tester bacteria prior to plating out. Significant mutagenic activity was found in a high proportion of samples (18 of 20). The histidine content in gastric juice which can affect in vitro mutagenicity testing must be adequately controlled before positive or negative results can be equated with the presence or absence of intragastric carcinogens.