The present study was carried out to investigate the effect of arsenic trioxide on the DNA and histomorphology of testis, liver and kidney of Swiss albino mice, Mus musculus. Oral administration of arsenic trioxide induced DNA damage in the testis, liver and kidney marked by light pink staining of nuclei after Feulgen's reaction with reduced fine chromatin. Simultaneously severe histological changes were noted like distortion of seminiferous tubules, disorganization of spermatogonia, spermatocytes and spermatids with cytoplasmic vacuolization and nuclear pycnosis in testis. There was almost disappearance of sinusoids due to disruption of hepatic plates, inflammatory cellular infiltration around central veins and cytoplasmic vacuolization in hepatocytes with large irregular nuclei in liver of treated mice. Disorganized glomeruli with distorted Bowman's capsules and mild to severe multifocal cloudy and hydropic degeneration with necrosis of tubules were observed in the kidney of treated mice. Inference drawn from the study indicated that arsenic induced both genotoxic histotoxic lesions.