High doses of progesterone can apparently inhibit secretion or release of hypophyseal hormones, including the luteotrophic hormone (LTH). Injection of progesterone into non-pregnant and pregnant guinea-pigs led to partial destruction of formed corpora lutea but did not prevent their initial formation. The data presented suggest that in the guinea-pig LTH is released about the time of ovulation, but for a period of less than 3 days. This temporary release of LTH is sufficient to initiate formation and function of corpora lutea. No further LTH support seems to occur in non-pregnant females. In pregnant animals, a neurohumoral signalling mechanism initiated by intrauterine events of implantation is assumed to call forth a second release of hypophyseal LTH, which is responsible for the maintenance of corpora lutea during the remainder of their functional life span during gestation. Prolactin is not luteotrophic in guinea-pigs.