In the adult ovary, pituitary FSH via interaction with its receptor (FSHR) is required for follicular maturation and granulosa cell development. In humans and nonhuman primates, the pool of follicles available for adult ovarian function is established in utero. However, our understanding of the ontogeny and developmental regulation of FSHR in the ovary of the primate fetus is incomplete. Our goal was to determine whether the baboon fetal ovary expresses the full-length FSHR mRNA transcript and whether levels are developmentally regulated. Fetal ovaries were obtained at mid (Day 100) and late (Day 165) gestation (term = Day 184) from untreated baboons and on Day 165 from baboons in which fetal estrogen levels were either decreased by >95% by treatment with the aromatase inhibitor CGS 20267 or restored to 30% of normal by treatment with CGS 20267 plus estradiol benzoate administered s.c. to the mother on Days 100-164. The full-length 2088-base pair FSHR mRNA transcript was expressed in ovaries of adult and fetal baboons untreated or treated with CGS 20267 or CGS 20267 and estrogen. Mean (+/-SEM) FSHR mRNA levels (ratio of FSHR mRNA:18S rRNA), quantified by reverse transcription polymerase chain reaction, were increased (P < 0.05) 2-fold between mid (0.34 +/- 0.06) and late gestation (0.76 +/- 0.07), an increase prevented (P < 0.05) in estrogen-depleted baboons (0.44 +/- 0.10) and partially restored by treatment with CGS 20267 and estrogen (0.58 +/- 0.16). We previously showed that the number of follicles/0.33 mm2 in fetal ovaries of untreated baboons in late gestation was reduced 50% by treatment with CGS 20267 and restored to normal in baboons treated with CGS 20267 and estrogen. Thus, when corrected for the number of follicles/0.33 mm2, FSHR mRNA levels were similar in baboon fetal ovaries untreated (0.010 +/- 0.001) or treated with CGS 20267 (0.009 +/- 0.002) or CGS 20267 and estrogen (0.007 +/- 0.003). We conclude that estrogen plays a major role in regulating ovarian FSHR mRNA expression in the primate fetus, and that the developmental increase in FSHR mRNA levels reflects the estrogen-dependent increase in folliculogenesis (i.e., increased number of granulosa cells and oocytes).