Isolated neurons from adult central ganglia of the snail Helisoma were cultured in vitro in modified Liebowitz L-15 medium. Such neurons displayed electrical excitability comparable to that in acutely dissected ganglia. Isolated neurons remained spherical in defined medium throughout culture durations up to 2 weeks. This static morphology was contrasted by the significant neuritic outgrowth which occurred from neurons maintained in medium with co-cultured intact Helisoma brains or in brain conditioned medium. A morphological sequence of growth cone formation and neurite extension occurred only in the presence of a conditioning factor(s) with a mode of action which included tight binding of the conditioning factor to the substratum. Under these conditions, the two primary neuronal phenotypes, electrical excitability and complex neuronal architecture, could be affected independently in adult molluscan neurons cultured in vitro.