The mutagenic potential of aqueous extracts of masheri (ME), chewing tobacco alone (CTE) and a mixture of chewing tobacco plus lime (CTLE) was tested using the Ames assay. ME exhibited mutagenicity in Salmonella typhimurium TA98 upon metabolic activation with aroclor-1254-induced rat liver S9, while nitrosation rendered it mutagenic in TA100 and TA102. CTE exhibited borderline mutagenicity in the absence or presence of S9 in TA98 and TA100 and after nitrosation in TA102, while nitrosation led to doubling of TA98 and TA100 revertants. In contrast, CTLE exhibited direct mutagenicity in TA98, TA100 and TA102, was mutagenic to TA98 upon S9 addition and induced mutagenic responses in all three tester strains after nitrosation. Experiments using scavengers of reactive oxygen species (ROS) suggested that CTLE-induced oxidative damage in TA102 was mediated by a variety of ROS. The high mutagenic potency of CTLE vis à vis that of CTE may be attributed to changes in the pH leading to differences in the amount and nature of compounds extracted from tobacco. Thus, exposure to a wide spectrum of tobacco-derived mutagens and promutagens may play a critical role in the development of oral cancer among users of tobacco plus lime.