Prorenin (PR) is present in high concentrations in the follicular fluid (FF) of the preovulatory follicle. It is the predominant form of renin detected in FF. Its biosynthesis and secretion from the ovary are regulated by gonadotropins. In the present study we measured PR and steroid levels in FF from 136 follicles. Follicular fluids were obtained, 36 h after hCG injection, from 41 ovarian-stimulated patients who underwent follicle puncture and oocyte retrieval for in vitro fertilization. We related FF PR to steroid levels and to the stage of oocyte-cumulus complex maturation. PR levels in 62 FF containing mature healthy fertilized oocytes averaged 2620 +/- 157 (+/- SE) ng/mL.h (728 +/- 44 ng/L.s; range, 1020-6880 ng/mL.h, 283-1911 ng/L.s). A subgroup of 16 of these follicles containing mature oocytes were from 7 women who conceived, in which PR levels spanned only the lower range from 1030-2720 ng/mL.h (286-756 ng/L.s). No patient conceived with FF PR above 2800 ng/mL.h (778 ng/L.s), yet one third of all mature follicles were above this range. Lower levels of PR were detected in FF containing immature oocytes (germinal vesicle stage) associated with either compact (1665 +/- 480 ng/mL.h; 463 +/- 133 ng/L.s; n = 22; P less than 0.02) or expanded (1785 +/- 193 ng/mL.h; 496 +/- 54 ng/L.s; n = 24; P less than 0.005) cumulus mass; a subgroup (n = 5) of follicles with immature oocytes and compact cumulus had very high levels of FF PR, ranging from 3830-7520 ng/mL.h (1064-2089 ng/L.s), while the remainder had levels less than 1300 ng/mL.h (361 ng/L.s). Progesterone and estradiol (E2) were lower in FF surrounding immature oocytes associated with compact (P less than 0.005) or expanded (P less than 0.02) cumulus, than in those containing mature oocytes. Testosterone (T) and androstenedione were measured in only a fraction of the samples; there were no apparent differences between follicles containing mature and immature oocytes. However, T and androstenedione levels were high in the subgroup of follicles containing immature oocytes and very high levels of PR. Of the hormones measured, T revealed the most striking relationship with PR (r = 0.62; n = 49; P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)