Benzo[a]pyrene (BP) and cyclopenteno[cd]pyrene (CPEP) are widespread environmental pollutants. CPEP is a relatively potent carcinogen in mouse skin with an activity second only to BP among environmental aromatic hydrocarbons. We have studied the combined application of BP and CPEP on mouse skin to determine their possible synergistic carcinogenic effect. Nine-week-old female Swiss mice in groups of 30 were treated on the back with high (H), medium (M) and low (L) doses, respectively, of 20 (H), 6.6 (M) or 2.2 (L) nmol BP or 200 (H), 66.6 (M) or 22.2 (L) nmol CPEP in 50 microliters acetone twice weekly for 48 weeks. Other groups received BP-H + CPEP-H, BP-M + CPEP-M, BP-L + CPEP-L, BP-H + CPEP-L, BP-M + CPEP-L, BP-L + CPEP-H, or BP-L + CPEP-M. A significant, 3- to 7-fold syncarcinogenic effect occurred when BP-M + CPEP-M were administered together. A smaller, but significant, synergistic effect (1.2- to 3.8-fold) was also observed when BP-M + CPEP-L or BP-L + CPEP-M was applied. Because of the syncarcinogenic effect of BP and CPEP, their abundance in engine emissions and ambient air samples may present a major source of carcinogenic risk.