Sodium azide was found to be mutagenic for Salmonella typhimurium by inducing base-pair substitutions that were not enhanced by pKM101 plasmid (R factor). However, the mutagenicity of sodium azide was decreased by enzyme proteins contained in rat-liver post-mitochondrial fractions, depending on the NADPH-generating system. Pre-incubation with human gastric juice also decreased azide mutagenicity. These metabolic effects might explain the conflicting nature of the mutagenicity and carcinogenicity tests reported in the literature. Laboratory reagents containing 0.1% sodium azide as a preservative showed the expected patterns of mutagenicity and of metabolic deactivation, and no aspecific interaction could be detected between azide and the various components, including proteins, of the reagents tested.