Prostacyclin (PG12), a potent vasodilator, is believed to be involved in increasing permeability within the wall of the preovulatory follicle. In ovarian hyperstimulation syndrome (OHSS), increased vascular permeability has been shown to lead to massive fluid accumulation in ovarian cysts and the peritoneal cavity. The objective of the in vitro and in vivo studies reported herein was to examine the production of 6-keto PGF1 alpha (a breakdown metabolite of PG12) during the luteal phase of women who develop OHSS, as well as the capacity of human granulosa luteal cells (GLC) obtained from stimulated in vitro fertilization (IVF) cycles to synthesize PGF1 alpha in vitro in long-term cultures. The in vivo results showed that during the luteal phase of women with OHSS, there is no increase in 6-keto PGF1 alpha production compared with the levels obtained from the luteal phase of normal ovulatory women. The GLC (representing early corpus luteum function) secreted significant amounts of 6-keto PGF1 alpha, but only in the first 48 hours of culture. Human chorionic gonadotropin (hCG) had no additional augmentative effect upon the production of 6-keto PGF1 alpha throughout the culture period. It is concluded that 6-keto PGF1 alpha is not produced in significant amounts during the luteal phase, and therefore PG12 probably does not play a major role in the etiology of OHSS.