The genetic activity of the structurally similar antitumor antibiotics anthramycin, tomaymycin and sibiromycin was evaluated in the standard Ames Salmonella/microsome mutagenicity assay, a Salmonella typhimun'um forward-mutation assay and the micronucleus test. None of the test drugs showed any significant genetic activity in forward or reverse Salmonella mutation assays. The ability of mouse-liver enzymes to produce mutagens from the drugs was examined in the Salmonella reverse-mutation assay and was generally negative. As the concentrations of sibiromycin increased, some activity was detected in the presence of liver S-9 fractions from Aroclor-induced mice. This observation could not be verified at higher concentrations in the reverse-mutation assay due to cytotoxicity, and in the forward-mutation assay due to interference with the selection process by S-9. Cytogenetic evaluation of anthramycin and tomaymycin in the micronucleus test also gave negative results. However, significant increases in the frequency of micronucleated polychromatic erythrocytes were observed in the bone marrow of sibiromycin-treated mice. The results suggest that, except for some possible activity of sibiromycin, these drugs are generally devoid of any marked genetic activity in the test systems employed.