The somatic muscle cells of the parasitic nematode Ascaris suum possess GABA receptors that gate chloride conductances in a similar fashion to the mammalian GABAA receptor subtype. These receptors mediate muscle relaxation and are the site of action of the anthelmintic piperazine. The properties of this receptor differ from the properties of the GABA-gated chloride receptors in the mammalian host, in particular they are not as sensitive to mammalian GABA receptor antagonists such as bicuculline and picrotoxin. Using two-electrode intracellular electrophysiological recording techniques from Ascaris muscle cells, we have tested the potency of a series of azole derivatives for their ability to block the chloride-dependent GABA response. The lead compound, SN606078, 2-(2,6-dichloro-4-trifluromethylphenyl)-4-(4,5-dicyano-lH-imidazol-2-yl)-2H-l,2,3-triazoIe, and 4 structurally related compounds reversibly blocked the conductance increase elicited by 30 μM GABA with IC50s of less than 10 μM. SN606078 (10 μM) decreased the slope of the dose-response curve for GABA, suggesting a non-competitive mechanism of action. In two-electrode voltage clamp experiments, 10μM SN606078 blocked the outward current elicited by 20 μM GABA in a voltage-dependent manner with 72 ± 2% inhibition at −20 mV and 49±6% inhibition at −40 mV. These observations indicate that SN606078 may act as an open-channel blocker of the GABA-gated chloride channel in A. suum.