The mutagenicity of coal dust and smokeless tobacco extracts was investigated in the Ames/Salmonella assay using strains with differing levels of O-acetyltransferase (OAT) and nitroreductase (NR) activity. Dichloromethane extracts of nitrosated and nonnitrosated coal dusts from West Virginia and New Mexico, and snuff and chewing tobacco were tested for mutagenicity using strains (TA-98) and YG1024 in the presence or absence of rat liver S9 mix. YG1024 contained multiple copies of the OAT gene; (TA-98) contained only a single copy of the OAT gene. Both strains contained similar levels of NR activity. The nonnitrosated snuff extracts were tested for mutagenicity in strains (TA-98/1,8-DNP6), (TA-98NR), (TA-98), YG1021, and YG1024 with or without the S9 mix. These strains contained varying amounts of OAT and NR activity. The nonnitrosated coal dust extracts were nonmutagenic. The nitrosated coal dust extracts were mutagenic under all conditions. The extracts were more mutagenic in strain YG1024 than in (TA-98). The presence of the S9 system increased their mutagenicity in YG1024 but not in strain (TA-98). The nonnitrosated tobacco products were mutagenic only in strain YG1024 when the S9 fraction was present, the snuff extract being more active. The nitrosated products were mutagenic under all conditions, except for the chewing tobacco extract when tested in strain (TA-98) without the S9 system. When tested in strains (TA-98NR), (TA-98/1,8-DNP6), (TA-98), YG1021, and YG1024 without S9 activation, the nonnitrosated snuff extract was active only in strain (TA-98NR). In the presence of S9 mix, the snuff extract was active in all strains. The degree of mutagenicity was related to the level of OAT activity in the tester strains not to the amount of NR activity. The strongest mutagenic response occurred in strain YG1024. The weakest response occurred in (TA- 98/1,8-DNP6) which lacked the OAT gene and had only a single copy of the NR gene. The authors conclude that when the levels of OAT activity are taken into account, the data suggest that the mutagenicity of the coal dust extracts is due to the presence of nitroarenes and the mutagenicity of the tobacco products reflects the presence of aromatic amines.