Twenty-two sarcomas were induced in 19 adult frogs (Rana pipiens) treated with 3-methylcholanthrene pellets. Thirteen of these tumors arose first in a denervated forelimb, and only 2 arose first in normal or nerve-supplemented control forelimbs (P = 0.004). The remaining tumors developed either as a second tumor in a tumor-bearing frog or in hindlimbs. The critical role of innervation in regenerative capacity suggests that the predilection to tumor formation in the denervated limbs may have resulted from their lessened regenerative capacity.