Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition was assessed by paired pulse activation of the perforant path input to the dentate gyrus. The measure of recurrent inhibition employed was the ratio of the population spike amplitudes of the responses to the first and second of the paired stimuli. Inhibition was assessed immediately before, and at 2, 24 and 120 hr following TMT. The results indicated a reduction in inhibition as early as 2 hr following treatment, suggesting that TMT-induced destruction of hippocampal pyramidal cells may be secondary to their over-activation from an uninhibited mossy fiber system.