We investigated the humoral mechanisms involved in tumour necrosis factor alpha (TNF alpha)-induced fever in rabbits. No change in lymphocyte-activating factor activity was detected in serum drawn during TNF alpha-induced fever. The pyrogenic activity of recombinant rabbit interleukin-1 beta (IL-1 beta) was entirely abolished by pre-incubation with anti-IL-1 beta antiserum from the goat. Fever induced by intravenous (i.v.) injection of IL-1 beta was significantly diminished by i.v. infusion of the antiserum. However, i.v. infusion of the antiserum for 1 h did not affect fever induced by i.v. injection of TNF alpha, when the antiserum infusion began either simultaneously with, or 2 h after, the injection of TNF alpha. Furthermore, intracerebroventricular injection of the anti-serum did not affect TNF alpha-induced fever. The intracerebroventricular administration of naloxone (an opioid receptor antagonist) significantly diminished TNF alpha-induced fever. The results suggest that IL-1, both in the blood circulation and in the brain, may not be involved in TNF alpha-induced fever. Similar to the contribution of eicosanoids, the opioid system in the brain seems somehow to contribute to the mechanism of the development of fever induced by TNF alpha in rabbits.