A method was developed to detect total mutagenicity of fried fish for S. typhimurium TA98, using Ames assay. Method described herein circumvented problems associated with the sample preparation for Ames assay, i.e., a multi-purification step of sample and interference with solvent residuals. Experiment A, the best method developed in the present study, consisted of two important steps: pH adjustment of the aqueous sample solution from fried fish samples to remove impurities, and simultaneous distillation extraction (SDE) for partially purified samples to remove volatile compounds from solvents. The procedure and results were described as below. Fillet of gizzard shad (Konosirus punctatus) fish sample fried for 10 min each side on the temperature-controlled fry-pan (210$circ$C) was homogenized in an aqueous acidic solution (pH 2) with a homogenizer, followed by filtration through Celite. The tiltrate (pH 2), removed some impurities by extraction with chloroform:methanol (2:1, v/v) mixture, was adjusted pH to 10 and then centrifuged to remove precipitate. The ethylacetate extract from the tiltrate of pH 10 was rotoevaporated and purified by SDE apparatus for 2 hours. Experiment A revealed significantly higher revertants (1928 per 25 g fried sample) than other Experiment (B, C, or D) tested. Experiment A gave good results in the mutagenicity test of fried fish sample with few purification steps using only 25 g fried sample and 650 ml of solvents; and thus this method could be a useful tool for the screening the mutagenicity or antimutagenicity of other foods as well.