Induction of neural differentiation in cultures of undetermined presumptive epidermis from three amphibian species was achieved by the addition of 1 millimolar dibutyryl adenosine 3',5'-monophosphate, 8-bromadenosine 3',5'-monophosphate, or adenosine C',E'-monophosphate together with theophylline. Adenosine 5'-monophosphate, adenosine 2',3'-monophosphate, dibutyryl guanosine 3',5'-monophosphate, and butyrate at 1 millimolar are ineffective. These results suggest that the action of the primary inductor or inductors may be mediated via adenosine 3',5'-monophosphate.