In sheep, the presence of an embryo in utero on the 12th to 13th day after oestrus prevents luteolysis. These studies investigated whether platelet-activating factor (PAF) could exert an antiluteolytic function, either alone or in combination with interferon. The intrauterine administration of 250 micrograms PAF per horn per day, administered through indwelling cannulae into the uterus as injections twice a day (n = 12) or by continuous infusion (n = 4) failed to extend luteal function compared with controls (n = 8). When indwelling cannulae were used to administer (i) 125 micrograms PAF per uterine horn, as a bolus infusion twice a day (n = 5), (ii) continuous infusion of 500 micrograms bovine recombinant alpha 1-interferon each day (brIFN, n = 5), (iii) 125 micrograms PAF per horn twice a day, plus 500 micrograms brIFN per day (n = 8), or (iv) vehicle (n = 5), the luteal phase was significantly longer in co-infused (iii) than in control (iv) animals. These findings indicate that pharmacological doses of PAF may act synergistically with interferons to prevent luteolysis.