The effects of the two cytokines, rat interferon-alpha, beta and human tumor necrosis factor-alpha, were studied at the rat neuromuscular junction by using classical electrophysiological techniques. Both cytokines in a similar way at concentrations of 2,000 and 35,000 U/ml, respectively, increased transiently and with a relatively long delay (15 to 25 min) the frequency of miniature endplate potentials. The observed effects may be related to complex second messenger mechanisms and contribute to modulation and plasticity of neurotransmission.