Intracerebroventricular injection of recombinant human interferon-alpha (IFN-alpha) in a dose of 1 x 10(4) U, but not 3 x 10(3) U, produced a long-lasting (at least for 60 min) increase (2.5-5 times the preinjection level) in the electrical activity of splenic sympathetic nerve filaments in urethane-alpha chloralose-anesthetized rats. Intravenous injection of IFN-alpha (3 x 10(4) U) also produced a similar excitation of splenic sympathetic nerves. There were no changes in arterial blood pressure and body temperature. The result, together with the previous findings, provides further evidence that the central IFN-alpha-induced suppression of cytotoxic activity of splenic natural killer cells may be mediated by the sympathetic innervation.