The GABA-related compound nipecotic acid is commonly used to inhibit GABA uptake. This report shows that nipecotic acid can also directly activate GABA(A)-like chloride channels. When applied to outside-out patches of paraventricular neurones, nipecotic acid (1 mM) activated inward unitary currents (approximately 3 pA at a holding potential of -60 mV, E(Cl)+44 mV). The EC(50) for ion channel activation was approximately 300 microM, 3 fold greater than that found for GABA itself in this preparation. The nipecotic acid activated channels had similar conductance and kinetic properties to those of GABA activated channels in the same patches, reversed near E(Cl) and were inhibited by bicuculline (3 microM). This study indicates that for experiments in which relatively high concentrations of nipecotic acid are used, possible direct GABA(A) receptor agonist properties should be considered.