Mutagenicities of Etoposide (VP 16-213) and Teniposide (VM-26), podophyllotoxin derivatives with antitumor activity, were studied by Rec-assay, Salmonella/microsome reverse mutation assay (Ames' test) and Micronucleus test. In the Rec-assay, both Etoposide and Teniposide showed positive results on B. subtilis H17 rec⁺ and M45 rec^-. They also induced the revertants of S. typhimurium TA 98, TA 1537 and TA 1538, but not of S. typhimurium TA 100, TA 1535 or E. coli WP2 uvrA in the Reverse mutation test. The results were not influenced by the addition of S-9 Mix. In the Micronucleus test, Etoposide and Teniposide induced significantly micronucleated polychromatic erythrocytes of the bone marrow cells in mice; 3.3-4.3% at the doses of 0.75-6 mg/kg and 4.0-6.1% at 0.5-4 mg/kg, respectively. These results indicate that Etoposide and Teniposide are both mutagenic.