Bovine interferon-alpha I1 has extensive sequence and functional homology with the antiluteolytic protein, bovine trophoblast protein-1. Because of the possible use of interferon-alpha I1 as a drug that supplements embryonic secretion of bovine trophoblast protein-1, interferon-alpha I1 was tested for other biological actions that might affect its usefulness as a fertility-enhancing treatment. Experiments were performed to evaluate whether interferon-alpha I1 causes hyperthermia and an acute depression in circulating concentrations of progesterone. In four experiments, intramuscular administration of interferon-alpha I1 (range 1.25 to 20 mg) caused hyperthermia; average peak body temperatures of 40 to 40.4 degrees C occurred 2.5 to 6 h after injection. Temperatures returned to baseline 12 to 16 h later. The rise in rectal temperature could be reduced, but not totally alleviated, with concomitant administration of an inhibitor of prostaglandin synthesis. The maximal hyperthermic response was similar when interferon-alpha I1 was delivered via osmotic minipumps or through a series of intramuscular injections. The hyperthermic response decreased with repeated daily exposure to interferon-alpha I1. The increase in rectal temperatures was associated temporally with a decrease in serum progesterone. Effects of interferon-alpha I1 on body temperature and circulating progesterone could possibly limit its effectiveness in enhancing fertility.