Twice daily oral thyrotropin-releasing hormone administered to female baboons throughout the menstrual cycle had no significant influence on cycle length or upon estrogen levels but produced blunted midcycle LH peaks and luteal phase progesterone levels in three fourths of the treatment cycles. Mean plasma prolactin levels were increased approximately 2.5-fold relative to untreated, ovulatory control cycles. CB-154 alone did not alter cycle length or endocrine parameters examined (mean prolactin levels were decreased but not significantly). Cycles during which CB-154 was administered concomitantly with TRH were characterized by normal ovulation as evidenced by luteal phase progesterone levels. Since the effect on LH secretion was reversed by concomitant CB-154 administration, TRH-induced anovulation in animals given long-term treatment appeared to be mediated through physiologic mechanisms sensitive to elevated circulating prolactin levels. However, this conclusion must be considered equivocal since prolactin levels were also elevated during ovulatory cycles following long-term TRH therapy. Finally, these data do no exclude the alternative possibility that anovulation in baboons given long-term TRH treatment was a reflection of thyroid disturbance and not directly attributable to elevated prolactin.