The effect of recombinant human tumor necrosis factor-alpha (rhTNF) on calcium currents of cultured neurons from neonatal rat superior cervical ganglia (SCG) was studied using whole-cell patch-clamp technique. We found that rhTNF-treated SCG neurons exhibited increased calcium current density without significant alteration in the steady- state parameters of activation and availability. The fraction of the current sensitive to dihydropyridines and omega-conotoxin also remained unchanged. Recovery from slow inactivation of the current, but not recovery from fast inactivation, was prolonged in rhTNF-treated cells when compared to that of control cells. We conclude that immune peptides such as rhTNF can alter cellular functions of sympathetic neurons via modulating ionic conductances. However, these changes observed in calcium currents of SCG neurons cannot account for the effect of rhTNF on norepinephrine secretion observed in a previous study. It is proposed that rhTNF exerts an additional effect at a later event in the exocytotic process.