The influence of the organophosphate, soman (pinacolyl methylphosphonofluoridate), on neuritic growth and substrate utilization by mammalian autonomic neural tissue was studied using explants of the rat superior cervical ganglion as a model. Soman produced a dose-dependent decrease in neuritic outgrowth from explants of this tissue maintained in a serum-free medium. Acetylcholinesterase in the explant as well as in culture media also decreased. In contrast, the effects of soman on explant metabolism were modest. Total protein and DNA content of the tissue was not affected. Only marginal changes in substrate utilization were detected; glucose use was unaltered, lactate production increased 20% with the highest soman tested. Soman increased the content of phosphocreatine in ganglion explants. This increase occurred in the absence of changes in the oxidation-reduction state of NAD calculated from pyruvate/lactate ratios. The results indicated that soman inhibited neuritic outgrowth from explants of the rat superior cervical ganglion in the absence of major effects on substrate utilization by this tissue.