Slices of hippocampus of the rat, preincubated with [3H]noradrenaline ([3H]NA), were used to investigated the effects of omega-conotoxin GVIA (omega-CTX) on the release of [3H]NA evoked by 3,4-diaminopyridine (3,4-DAP, 200 microM), veratridine (0.7 microM) or monensin (0.01 microM) in the absence of extracellular CA2+. The 3H outflow, evoked by 3,4-DAP or veratridine, was inhibited by tetrodotoxin (TTX) or omega-CTX but the 3H outflow evoked by monensin was neither affected by TTX nor by omega-CTX in Ca(2+)-free medium, containing 1 mM EGTA. The release response to 3,4-DAP or veratridine was also blocked by omega-CTX in a concentration-dependent manner in Ca(2+)-free medium, containing 2.5 mM Mg2+ and the blockade was still complete after washing for 20 min with omega-CTX-free medium. The findings suggest that, under these conditions, the toxin might also block sodium channels.