The slow intravenous infusion of amphotericin B (amB) induced a moderate, partially dose-dependent fever in male adult rabbits, whereas the iv bolus injection of the drug was less pyrogenic and only at higher doses. Higher, more sustained fevers occurred with doses of 2.5 and 5.0 mg of amB. The threshold pyrogenic dose of amB in the rabbits tested approached 0.16 mg per Kg (delta T greater than 0.4 degrees C). Endotoxin-tolerant rabbits had a lower increase in rectal temperature when challenged with amB. No fever occurred in mice treated with amB.