Effects of recombinant interferon-alpha (IFN-alpha) on the single activity of thermosensitive and thermally insensitive neurons in the preoptic and anterior hypothalamus (PO/AH) were investigated in rat's brain tissue slices. IFN-alpha, in doses of less than 5 x 10(3) U/ml, decreased the activity in 34 of 52 warm-sensitive neurons and increased the activity in 3 of 5 cold-sensitive neurons, but had no effect on the majority (12 of 17) of thermally insensitive neurons. The neuronal responses to local IFN-alpha could be observed in a Ca2+-free/high Mg2+ solution, suggesting the direct action of IFN-alpha. The actions of IFN-alpha on thermosensitive neurons were blocked by concurrent application of naloxone, but not by sodium salicylate in doses which effectively blocked the neuronal responses to endotoxin and leukocytic pyrogen in the previous studies. The fever induced by IFN-alpha may be explained, at least partly, by the direct actions of IFN-alpha on the PO/AH thermosensitive neurons, which involve the opiate receptor mechanisms.