'Shamma', also known as Yemeni snuff, is frequently used as a chewing material in Yemen and some parts of Saudi Arabia. Preliminary clinical observations indicated that long-term users of 'shamma' may develop oral cancer. A battery of in vitro bioassays were, therefore, used to test genotoxicity of this substance. The test systems included the histidine reversion assay in Ames' Salmonella strains, induction of aberrant colonies and tryptophan gene conversion in the D7 diploid strain of Saccharomyces cerevisiae, and oncogenic transformation of C3H mouse embryo 10T1/2 cells. Data indicated that direct-acting mutagen(s) were present in a chloroform extract of the powdered 'shamma' resulting in positive effects in all of the test systems used. Using high-performance liquid chromatography (HPLC), three major fractions were separated from the extract, of which two were found to be mutagenic.