These studies investigate whether the neurosteroid and 5α-reduced metabolite of testosterone (T), 5α-androstane-3α,17β-diol (3α-Diol), has anti-seizure effects similar to its parent compound. In experiment 1, ovariectomized (ovx) Long-Evans rats (n=20) were subcutaneously (SC) administered 32 mg/kg kainic acid or saline vehicle 10 min following 0.0, 3.0, or 7.5 mg/kg 3α-Diol in 10% ethanol, propylene glycol vehicle (veh). During 2 h of observation of ictal activity, 3α-Diol (3.0 and 7.5 mg/kg) prior to kainic acid significantly decreased the number and duration of partial and full seizures compared to the 0.0 3α-Diol conditions and produced ictal activity that was comparable to 0.0 mg/kg 3α-Diol no kainic acid controls (procedure controls). Animals that received 7.5 mg/kg 3α-Diol prior to kainic acid had shorter latencies and distances to the hidden platform in a Morris Water Maze task than those that received 0.0 3α-Diol, 1 week following ictal activity. Administration of 3α-Diol (3.0 or 7.5 mg/kg) prior to kainic acid stimulation resulted in a greater number of identifiable neurons in the hilar region of the hippocampus, compared to 0.0 3α-Diol condition. Experiment 2 was conducted to ascertain whether 3α-Diol’s anti-seizure effects were comparable to T and possibly a result of metabolism from T. Ovx rats (n=36) were stereotaxically implanted with bipolar electrodes into the perforant pathway. One hour prior to perforant pathway stimulation, six rats were SC injected with either T (7.5 mg/kg), 3α-Diol (7.5 mg/kg), 7.5 mg/kg T+4MA (a 5α-reductase inhibitor, 17β-N,N-diethylcarbamoyl-4-methyl-4aza,5α-androstan-3-one), 4MA alone, 10% propylene glycol vehicle (veh) with perforant pathway stimulation, or veh without perforant pathway stimulation. 3α-Diol and T produced similar seizure activity, water maze performance, and neuronal integrity in the hilar region of the hippocampus that were comparable to unstimulated controls. Because the T and 3α-Diol groups were not different from T+4MA but tended to be different from 4MA alone on these measures, this suggests that 3α-Diol and T can have similar anti-seizure effects which may be due to actions of neurosteroids. © Published by 1998 Elsevier Science Ltd. All rights reserved.