Ovulation in mammals involves pulsatile release of GnRH from the hypothalamus into the hypophyseal portal system with subsequent release of LH from the anterior pituitary into systemic circulation. Elevated circulating concentrations of LH induce a cascade of events within the mature follicle, culminating in follicle rupture and evacuation. The broad classification of species as either spontaneous or induced ovulators is based on the type of stimulus responsible for eliciting GnRH release from the hypothalamus. In spontaneously ovulating species (e.g., human, sheep, cattle, horse, pigs), release of GnRH from the hypothalamus is triggered when, in the absence of progesterone, systemic estradiol concentrations exceed a threshold. In induced ovulators (e.g., rabbits, ferrets, cats, camelids), release of GnRH is contingent upon copulatory stimuli; hence, ovulation is not a regular cyclic event. Since a classic 1970 Peruvian study, dogma has maintained that physical stimulation of the genitalia during copulation is the primary trigger for inducing ovulation in alpacas and llamas. Exciting results of recent studies, however, provide direct evidence for the existence of an ovulation-inducing factor (OIF) in semen, and compel us to re-examine the mechanism of ovulation in both induced and spontaneous ovulators. Ovulation-inducing factor in seminal plasma is a potent stimulant of LH secretion, ovulation and luteal gland development, and acts via a systemic rather than a local route. OIF is a protein molecule that is resistant to heat and enzymatic digestion with proteinase K. It has a molecular mass of 14 kDa, and may be part of a larger protein complex or pro-hormone. The effect of OIF is dose-related and evident at physiologically relevant doses (i.e., as little as 1/100th that present in the ejaculate), and is mediated, in whole or in part, at the level of the hypothalamus in vivo. The factor exists in the seminal plasma of every species in which it has been examined thus far, including Bactrian camels, alpacas, llamas, cattle, horses, pigs, and koalas. Seminal plasma OIF does not appear to be a phylogenetic vestige in spontaneous ovulators since it (1) induced ovulation in pre-pubertal mice, (2) altered ovarian follicular wave dynamics in cows, and (3) elicited LH release in vitro from primary pituitary cell cultures of rats, mice, guinea pigs, rabbits, llamas and cows. (C) 2012 Elsevier B.V. All rights reserved.