Denervation-induced alterations in the composition of the soluble protein population of various stages of forelimb regenerates in the adult newt were examined. Denervation alters the normal protein arrays in three ways: (1) proteins may be eliminated from an array, (2) proteins not normally present in an array may be induced to appear, and (3) proteins unique to denervated regenerates may appear in an array. The character of the denervation-induced alteration at five days post-amputation is basically different from that at later stages of regeneration. The stages during which the regenerate is becoming independent of the nerve for its morphogenetic activity are the ones in which the protein profiles are the most drastically altered. Morphogenetic independence of the nerve therefore does not require the synthesis of nerve-dependent proteins, and it is concluded that nerve independence is a property generated by the production of a critical number of blastema cells. Nerve-dependent proteins are required for the mitotic activity which leads to attainment of the critical mass, and the failure of denervated early regenerates to continue regeneration may be due solely to mitotic inhibition.