PIP: Medroxyprogesterone (MPA) is a progestin with no clinically detectable estrogenic and androgenic properties used in the treatment of sexual precocity. This report presents the results of administering large intramuscular doses of MPA (200 to 300 mg every 7 to 10 days for periods ranging from 5 to 40 months) in 3 girls and 1 boy with rapidly progressing idiopathic sexual precocity (e.g., breast enlargement, penile enlargement, pubic hair growth). Urinary steroids were measured by bioassay, standard modification of the double isotope derivative method, and other standard methods. The MPA regimen suppressed the signs and symptoms of precocious puberty. The 3 girls did not have further menstrual flow, breast tissue regressed, uterine size decreased, and vaginal cornification diminished, although not to prepubertal levels. A marked decrease in frequency of erections, no further penile enlargement, and only minimal progression of sexual hair were observed in the boy (the testis continued to enlarge, however). Excessive weight gain, rapid rate of linear growth and skeletal maturation were observed in the children during treatment, as was blood pressure elevation. The effectiveness of MPA appears to be mediated by the suppression of pituitary gonadotropin secretion. However, there was no consistent reduction of urinary gonadotropin levels, and suppression of gonadal stimulation was incomplete. Evidence of drug toxicity precludes further administration of high dosages of MPA even for research purposes.