To determine if differences in acrylamide distribution or binding to DNA could be responsible for the reported higher incidence of skin papillomas observed after oral administration compared to topical application, 14C-acrylamide was administered by topical application and oral intubation to male SENCAR and BALB/c mice. Portions of lung, liver, stomach, testes and skin were removed, and 14C measured at 15 min, 30 min, 1, 6, 12, 24 and 48 hours. Binding to DNA, RNA and protein was measured at 6 and 48 hours. Following oral administration, few strain differences in distribution or binding were noted. After topical application, SENCAR mice generally showed higher tissue levels than did the BALB/c mice at the early time periods but not at the later ones. Comparing the two routes, comparable levels were observed in all tissues except the skin where the amount of 14C-acrylamide after topical application was approximately 100 times that observed after oral administration.