delta-Conotoxins are a family of small, disulfide-rich peptides found in the venoms of predatory cone snails (Conus). We examined in detail the effects of delta-conotoxin PVIA from the fish hunting cone snail Conus purpurascens on sodium currents in dissociated sympathetic neurons from the leopard frog Rana pipiens. We also compared this toxin's effects with those of delta-conotoxin SVIE from Conus striatus, another piscivorous cone snail. d-PVIA slowed the time-course of inactivation of delta sodium currents and shifted the voltage-dependence of activation and steady-state inactivation to more hyperpolarized potentials. Similar, albeit more pronounced, effects were seen with d-SVIE. While the effects of d-PVIA were reversed by washing, those of d-SVIE were largely irreversible over the time-course of these experiments. The effects of d-PVIA could be suppressed by conditioning depolarizations in a voltage- and time-dependent manner, whereas the effects of d-SVIE were largely resistant to conditioning depolarizations. Last, in intact sympathetic nervous system preparations, d-PVIA inhibited evoked trains of compound action potentials. Many of these effects of d-PVIA and d-SVIE are remarkably similar to those of toxins that bind to site 3 on voltage-gated sodium channels.