It is known that nerves are particularly critical during the early or dedifferentiative phase of limb regeneration. During this period in the innervated limb, cells just proximal to the amputation surface dedifferentiate, migrate to the limb tip, and undergo mitosis. These processes give rise to a population of undifferentiated mesenchymatous cells capable of redifferentiating into the missing components of the newly forming regenerate. The consequences of denervation stand in stark contrast to the normal events occurring in the innervated limb, because neither a blastema nor a regenerate forms. Results from this study indicate that during the early portion of the dedifferentiative phase in regenerates less than 2 3/4, days old the nerve apparently has little or no effect on the internal stump tissues. Of considerable interest in this regard is this study's documentation of a lack of neural influence on DNA synthesis and thus the cell cycle during the early dedifferentiative phase. Subsequently, during a transition period represented by 2 3/4 to 5 1/2 days regenerates there is some evidence for a neural influence on DNA synthesis in cells of the limb stump. Finally, on days 6 through 8, DNA synthesis is clearly nerve dependent. Since DNA synthesis is a prerequisite for mitosis, the depressed synthesis in a denervated limb precludes mitotic activity during the nerve-dependent, later portion of the dedifferentiative phase. Therefore, this research supports the idea that during the late dedifferentiative phase, including mound and early cone blastemal stages, there is a neural influence on the G1 or S phases of the cell cycle. This conclusion thereby makes progress toward explaining earlier observations of depressed mitotic activity during this period.