The effects of 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) and phenobarbital (PB) on synaptic excitation and inhibition in rat hippocampal slices in vitro were compared. Stimulations were made orthodromically and antidromically while we recorded extracellularly from the dendritic and the somatic layer of the CA1 region. Perfusion with 5 micrograms/ml of 3 alpha-OH-DHP for 30 min significantly increased the recurrent inhibition evoked by antidromic stimulation. The effect was most pronounced at short interstimulus intervals. The duration of the recurrent inhibition also was prolonged. There was no effect on the conditioned population spike after orthodromic paired-pulse stimulation. Furthermore, no effect was observed on the amplitude of the orthodromic fiber volley, the rate of increase in the field excitatory postsynaptic potential (EPSP) and the latency and amplitude of the CA1 population spike. Qualitative and quantitative similar findings were observed during perfusion with PB 0.1 mg/ml, (i.e., a concentration 20 times higher than that of 3 alpha-OH-DHP). Higher concentrations of PB also affected synaptic excitation. The findings suggest a similar effect of 3 alpha-OH-DHP and PB on recurrent GABA-ergic inhibition; however, 3 alpha-OH-DHP appears to be much more potent.