Women with complaints of moderate or severe dysmenorrhea received intrauterine progesterone contraceptive system (16 patients) or placebo systems releasing no hormone (8 patients). Tampons were collected during the period prior to insertion and from 11 and 6 women, respectively, in the two groups at the second and fourth postinsertion periods. Prostaglandins in menstrual blood were extracted, and the amount and concentration of PGF2alpha analyzed for each patient. The menstrual blood loss (MBL) was determined by the method of Hallberg and Nilsson. The total PGF2alpha content was significantly lower in the group using progesterone systems than in the placebo group at collections 2 and 4 and was well below the preinsertion level; in placebo users the content tended to be slightly higher than it had been before insertion. The MBL increased approximately 60% above preinsertion levels in five of the six women using placebo units and decreased approximately 40% in 10 of 11 women with progesterone systems. Of the eight women in the progesterone group who had reported severe dysmenorrhea prior to insertion, seven reported an improvement; three of six in the placebo group reported a lower degree of improvement. These findings suggest that the decreased biosynthesis of PGF2alpha is a concomitant of intrauterine progesterone administration and may be a basis for the ability of the Progestasert system to diminish menstrual pain.