The neuroblastoma × glioma hybrid cell line NH15-CA2 was used to test the effects of two interleukins on neuronal Na⁺ channels. The cells were cultured in the presence of dibutyryl cAMP and retinoic acid, which yielded a high expression of Na⁺ channels so that the cells were excitable. Na⁺ currents were triggered and recorded in the whole-cell recording mode. Comparison of the effects of tetrodotoxin and μ-conotoxin established that the expressed Na⁺ channels were of the neuronal type. Bath-applied recombinant human interleukin-2 (rIL-2) had a reversible inhibitory effect on the Na⁺ currents, although to a lesser extent than on muscular Na⁺ currents (more than 1000 U/ml required for 50% block in NH15-CA2 cells vs 500 U/ml in myoballs). The current/voltage relationship was not affected by the presence of rIL-2, but the steady-state inactivation curve was shifted by –7.7 ± 4.8 mV (mean ± SD, n=18). Recombinant human interleukin-1β (rIL-1β), applied at 1000 U/ml, showed an inhibitory effect on the Na⁺ currents in about one-third of the cells tested. The mechanism of inhibition was different from that of rIL-2, as rIL-1β seemed to cause a block without affecting voltage dependence or kinetics of the channels.