The tumorigenicity of benz[c]acridine (B[c]ACR) and a number of its derivatives, including the five metabolically possible trans-dihydrodiols, the diastereomeric bay-region diol-epoxides, two non-bay-region diol-epoxides, and the K-region 5,6-oxide, were assessed in newborn mice. A total dose of 0.50 or 1.05 µmol of compound was administered i.p. to preweanling mice, and tumorigenic activity was determined when the mice were 33 to 37 weeks old. B[c]ACR was a weak carcinogen producing an average of 2.5 lung tumors/mouse and 0.15 liver tumor/male mouse at the 1.05-µmol dose. Of the five metabolically possible trans-dihydrodiols of B[c]ACR, only trans-3,4-dihydroxy-3,4-dihydro-B[c]ACR (B[c]ACR 3,4-dihydrodiol) had high tumorigenic activity. B[c]ACR 3,4-dihydrodiol induced 2- and 10-fold more pulmonary and hepatic tumors, respectively, than did the parent compound while the trans-1,2-, 5,6-, 8,9-, and 10,11-dihydrodiols had very little or no tumorigenic activity. Both of the diastereomeric bay-region 3,4-diol-1,2-epoxides, in which the epoxide oxygen is either cis (isomer 1) or trans (isomer 2) to the benzylic hydroxyl group, had tumorigenic activity. Isomer 2 was the most tumorigenic derivative tested, inducing at least 60, 7, and 12 times more lung tumors per mouse than did isomer 1, B[c]ACR 3,4-dihydrodiol and B[c]ACR, respectively. The K-regton 5,6-oxide and two non-bay-region diol-epoxides (isomer 2 of B[c]ACR 8,9-diol-10,11-epoxide and B[c]ACR 10,11-diol-8,9-epoxide) were weakly active or inactive at the dose tested. The demonstration that B[c]ACR 3,4-diol-1,2-epoxide-2 is exceptionally tumorigenic and that its metabolic precursor, B[c]ACR 3,4-dihydrodiol, is more active than the parent hydrocarbon, B[c]ACR, support the concept that isomer 2 of the bay-region diolepoxide may be an ultimate carcinogenic metabolite of B[c]ACR.