The effect of thiopental on rat brain hippocampal GABA receptors was studied in slice preparations and membrane fractions. In slice preparations, thiopental at a concentration of 10(?5) M enhanced the GABA (1?5 x 10(?4)M) inhibition of the field potentials evoked in pyramidal neurons by stratum radiatum stimulation. In hippocampal slices obtained from chronically barbital-administered (100 mg/kg, b.i.d., 10 days) rats, less enhancement of thiopental on GABA inhibition of the field potentials was observed. In binding experiments, two components of specific [(3)H]GABA binding to membrane fractions were observed. While thiopental was without effect on high-affinity sites, [(3)H]GABA binding with low affinity was enhanced by 80% in the presence of 10(?5) M thiopental. The results are discussed in relation to the phenomena underlying chronic barbiturate administration.