In this study, genotoxic effects of tributyltin (TBT) and methidathion (MD) were investigated using Drosophila wing somatic mutation and recombination test (SMART). This test is based on the principle that the loss of heterozygosity of suitable recessive marker hairs such as multiple wing (mwh) and flare-3 (flr(3)), can lead to the formation of mutant clones of larval cells, which are then expressed as spots on the wings of the adult flies. Third-instar larvae that were trans-heterozygous for the two genetic markers mwh and flr(3) were treated at different doses (0,1 mg/L, 1 mg/L, 10 mg/L, 30 mg/L, and 50 mg/L of TBT and 0.01 mg/L, 0.025 mg/L, 0.05 mg/L, 0.06 mg/L, and 0.075 mg/L of MD) of the test compounds. Mitomycin C (MMC), a commonly known mutagen, was used as positive control. The results indicated that highest experimental dose of TBT showed toxic and genotoxic effects, including recombinogenic activity in the marker-heterozygous flies. However, based on our results, MD showed no genotoxicity in the SMART assay, an in vivo model.