The profile of circulating progesterone concentration is more dynamic in cattle than in horses. Greater prominence of progesterone fluctuations in cattle than in horses reflect periodic interplay in cattle between pulses of a luteotropin (luteinizing hormone; LH) and pulses of a luteolysin (prostaglandin F2alpha; PGF2alpha). A dose of PGF2alpha that induces complete regression of a mature corpus luteum with a single treatment in cattle or horses is an overdose. The overdose effects on the progesterone profile in cattle are an immediate nonphysiological increase taking place over about 30 min, a decrease to below the original concentration, a dose-dependent rebound 2 h after treatment, and a progressive decrease until the end of luteolysis. An overdose of PGF2alpha in horses results in a similar nonphysiological increase in progesterone followed by complete luteolysis; a rebound does not occur. An overdose of PGF2alpha and apparent lack of awareness of the rebound phenomenon has led to faulty interpretations on the nature of spontaneous luteolysis. A transient progesterone suppression and a transient rebound occur within the hours of a natural PGF2alpha pulse in cattle but not in horses. Progesterone rebounds are from the combined effects of an LH pulse and the descending portion of a PGF2alpha pulse. A complete transitional progesterone rebound occurs at the end of preluteolysis and the beginning of luteolysis and returns progesterone to its original concentration. It is proposed that luteolysis does not begin in cattle until after the transitional rebound. During luteolysis, rebounds are incomplete and gradually wane. A partial rebound during luteolysis in cattle is associated with a concomitant increase in luteal blood flow. A similar increase in luteal blood flow does not occur in mares.