A mutagenic response was obtained in the Sal-monella /microsome reversion test by preincubating sodium nitrite and cimetidine in human gastric juice from untreated individuals, or even by adding nitrite to gastric juice samples from patients receiving cimetidine. Both base-pair substitutions (strains TA1535 and TA100) and, though very weakly, also frame-shift errors (TA1537, TA1538 and TA98) were induced by such reaction. Mutagenicity was not affected by S-9mix containing rat liver homogenates, neither in the sense of activation nor of deactivation. The optimal reaction occurred at high equimolar concentrations of the two precursor compounds, under physiological pH and temperature conditions and within a short time of contact. Ascorbic acid was efficient in preventing the formation of mutagenic nitroso-derivative(s)