Groups of 50 B6C3F1 mice of each sex were given 0.012% or 0.006% phenytoin in their powdered diet for 78 wk and were then fed a basal diet for 8 wk. Control groups of 50 mice of each sex were fed powdered basal diet for 86 wk. Mean total intakes of phenytoin per mouse were 301 and 150 mg in males, and 292 and 154 mg in females, respectively. The survival rates of each group at week 86 were 72-86% in males, and 86-94% in females. Liver-cell tumors, alveolar tumors, and Harderian-gland adenomas in male mice, malignant lymphomas and/or leukemias in female mice, and a few tumors in other organs of both sexes were found. The total number of hepatocellular tumors in mice treated with the high dose of phenytoin was significantly smaller than that of control mice in males (p less than 0.05). However, hepatocellular carcinomas developed 15 to 3 wk earlier in a few mice of phenytoin-treated males than in the controls. In other organs, no significant increase of any particular tumor type was observed in the treated groups of both sexes. Thus, phenytoin was not carcinogenic in B6C3F1 mice in this study.