The present study determined whether morphological differentiation of placental villous cytotrophoblasts into syncytiotrophoblast during primate pregnancy was developmentally regulated and whether oestrogen has a role in this process. Placental volumetric composition of the cytotrophoblast and syncytiotrophoblast was determined by the test-point counting method on days 45-54, 60, 100, and 170 of gestation (term=184 days) in untreated baboons, on day 60 after placental oestrogen production was prematurely elevated by administration of aromatizable androstenedione or oestradiol, and on day 170 after oestrogen production was suppressed by administration of aromatase inhibitor CGS 20267. Cytotrophoblast and syncytiotrophoblast volumes and oestrogen levels increased (P< 0.01) with advancing gestation. Due to the rise in syncytiotrophoblast volume (12-fold) exceeded that of the cytotrophoblast (threefold), the mean (sem) ratio of syncytiotrophoblast and cytotrophoblast volumes increased (P< 0.001) from 3.4 (0.5) ml on day 60 to 12.1 (2.8) ml on day 170. Androstenedione administration elevated serum oestradiol levels threefold (P< 0.01) and increased the ratio of syncytiotrophoblast: cytotrophoblast volumes on day 60 by 50 per cent (P< 0.03) to that normally observed on day 100. However, the ratio of trophoblast volumes was unaltered in oestradiol-treated and CGS 20267-treated baboons. It is concluded that there is a developmental increase in morphological differentiation of the placental villous trophoblast during primate pregnancy and that androstenedione potentially via its conversion to oestrogen has a role in this process.