Clozapine and several other antipsychotic/antidepressant drugs that fully or partially block GABAA receptors were tested at concentrations that reversed the inhibitory effect of 1 μM GABA on 35S-t-butylbicyclophosphorothionate ([35S]TBPS) binding to rat forebrain membranes only about 20–30%, here designated “core” fractions. Clozapine at 10 μM reverses 1 μM GABA 25 ± 4.0% (n = 23) (its “core” fraction). Fourty three compounds were tested alone, and pairwise together with 10 μM Clozapine. The “core” fractions of some of the compounds yielded significant additive reversals together with 10 μM Clozapine, while others did not. A group of 14 compounds of which 7 are clinically effective antipsychotic drugs, including Chlorprothixene, Clomacran, Clopipazan, Fluotracen, Sulforidazine, Thioproperazine, and cis-Thiothixene, were statistically non-additive with 10 μM Clozapine, suggesting that all of these drugs selectively block the same core population of GABAA receptors as Clozapine. These non-additivities also suggest that Clozapine at 10 μM fully saturates a subset of GABAA receptors blocked by 1 μM GABA. Therefore, Clozapine probably blocks 2 or more types of GABAA receptors, but only half of the receptors that are sensitive to 1 μM GABA. A second group of 12 compounds of which 6 are clinically active antidepressant/antipsychotic drugs including Amoxapine, Clothiapine, Dibenzepine, Inkasan (Metralindole), Metiapine and Zimelidine were slightly, but significantly, additive with Clozapine suggesting that these compounds block most of Clozapine's core fraction, plus a small additional fraction. A third group consisted of ten compounds that yielded larger (R > 80) and statistically highly significant additivities with Clozapine. Complete additivity was obtained with Bathophenanthroline disulfonate, and Isocarboxazid, suggesting that they block GABAA receptors other than those blocked by 10 μM Clozapine. Seven “classical” GABAA receptor blockers, also tested at concentrations yielding 21 to 33% reversal alone, were all significantly additive with 10 μM Clozapine, but in no case was the additivity complete. The largest additivity was obtained with Pitrazepine (21%) and the smallest with Tubocurarine (9%). These results provide further support for the notion that selective blockade of the same subset of GABAA receptors may contribute to the clinical antipsychotic/antidepressant effects of Clozapine. The ΔBopt values for Clozapine are 50 ± 1.7% and 26 ± 2.6% ( n = 3) in whole rat forebrain and cerebellum, respectively, confirming that clozapine-sensitive GABAA receptors are unevenly distributed in the brain. The sedative and anxiolytic properties of Clozapine and other antipsychotic drugs may be due to selective blockade of GABergic disinhibition at certain interneurons.