In slices of rat cuneate nucleus, responses to the GABA-A receptor agonist muscimol were potentiated by flurazepam. The maximal potentiation by 1 microM flurazepam was antagonized by the neuronal benzodiazepine receptor ligand Ro15-1788 3 microM, by the quinoline derivative PK8165 0.1 microM and by the peripheral-type benzodiazepine receptor ligand Ro5-4864 0.1 microM. Another ligand for the peripheral-type benzodiazepine receptor, PK11195 10 microM, enhanced the potentiating effect of a submaximal concentration of flurazepam 0.1 microM and prevented the antagonism of flurazepam by Ro5-4864. At much higher concentrations of these drugs, additional effects were seen. Ro15-1788 30 microM and PK11195 30 microM each caused small potentiations of muscimol while Ro5-4864 30 microM caused a small antagonism. Ro15-1788 30 microM, PK8165 100 microM and Ro5-4864 30 microM all antagonized the potentiation of muscimol by pentobarbitone 10 microM; also, PK8165 and Ro5-4864 enhanced the potency of picrotoxin as an antagonist of muscimol. It is concluded that both Ro5-4864 and PK8165 have several distinct effects on the GABA-A receptor complex, all of which could result in reduced responses to muscimol.