The Salmonella/microsome assay with strains TA97, TA98, TA100, and TA102 was used to examine the potential mutagenicity and structure-activity of 16 mono- and dihalogenated pyridines. The chemical reactivity of the halopyridines suggests that nucleophilic displacement of halogens can occur with halogens at positions 2, 4, and 6 being displaced in addition-elimination reactions. 2-Chloropyridine gave a positive result with rat liver metabolic activation, and 2-fluoropyridine gave equivocal results under these conditions. Mutagenic responses were also obtained with 2-chloromethyl pyridine and 3-chloromethyl pyridine, both in the presence and absence of rat liver S-9. These results suggest the halogenated pyridines, especially with halogens at the 2-position, and singly on a methyl substituent, have mutagenic activity in the Salmonella assay.