Intrauterine and intramuscular administration of interferon was tested for effectiveness in extending luteal lifespan in cattle. Intrauterine infusion of 1 mg of recombinant bovine interferon-alpha I1, twice daily, to lactating dairy cows from d 14 to 21 after estrus extended interestrous interval (30.4 +/- 1.91 d versus 24.8 +/- .58 d) and functional lifespan of the corpus luteum (28.4 +/- 2.01 d versus 23.6 +/- .75 d). In another experiment, twice daily intramuscular injection of 20 mg interferon to Simmental heifers from d 15 to 19 extended interestrous intervals (24.6 +/- 1.36 d versus 20.6 +/- .49 d) and functional lifespan of the corpus luteum (23.2 +/- .37 d versus 20.2 +/- .73 d). In a third experiment, pubertal dairy heifers received twice daily intramuscular injections of 0, 2.5, 5.0, or 10.0 mg/injection of interferon from d 14 to 21 after estrus. The three interferon-treated groups had longer interestrous intervals and functional luteal lifespans than the control group. Interestrous intervals were 22.0 +/- .68, 24.0 +/- 1.14, 24.6 +/- 1.17, and 25.4 +/- .97 d, respectively. The present data strengthen the theory that an interferon-alpha-like molecule can regulate luteal function in cattle. Such a regulatory compound might prove useful in schemes to reduce embryonic mortality caused by aberrant secretion of embryonic interferon.