Using electron microscopy, the appearance of fenestrations within blood vessels of the fetal sheep pituitary gland was studied at 40, 80 and 122 days of gestation (term = 150 days). While fenestrations were extremely rare at 40 days of gestation, blood vessels contained characteristic regions of narrow endothelium, termed attenuations. There was an increase in the frequency of fenestrations with increasing gestational age, while there was a decrease in the number of attenuations, to the extent that the latter were not observed at 122 days of gestation. In order to examine the ‘leakiness’ of vessels with relatively few fenestrations, the fate of intracardially injected horseradish peroxidase (HRP) was studied in 50- and 51-day fetuses. Flocculant HRP reaction product was observed in the lumen of pituitary blood vessels, within endothelial cells, as well as within perivascular spaces and intercellular spaces between pituitary glandular cells. HRP was also observed in internalised vesicles within pituitary cells. These results indicate that even though fenestrations are scarce at early gestational ages, blood-borne substances can leave the portal network to interact with pituitary cells. The previously reported patency of the portal vascular system in the immature fetus is supported by our observations.