Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.