6 nitrosamines, 5 of which cause rat nasal cancer, were tested for mutagenicity in the TA100 strain of S. typhimurium with rat and rabbit nasal, lung and liver S9 homogenates. The TA98 strain also was used with rabbit tissue homogenates. The two cyclic nitrosamines tested, N-nitrosopiperidine and N-nitrosopyrrolidine, were substantially mutagenic with all rabbit tissue homogenates in TA100, but in the rat only nasal homogenate was effective in activating them. N-Nitrosodi(n)propylamine also was activated by rat nasal tissue homogenate but not by the other rat or rabbit tissue homogenates. Diethanolnitrosamine was a direct mutagen in both TA100 and TA98. N-Nitrosodimethylamine and N-nitrosodiethylamine were not mutagenic under any test conditions. The results indicate that some nitrosamines that cause nasal cancer can be activated by nasal enzymes and that possibly important differences in activating capabilities occur among respiratory tract and hepatic tissues and among animal species.