Hydrops fetalis, with or without oligo- or polyhydramnios, is associated with very high fetal mortality. In many cases the causes are unknown. Chronically cannulated ovine fetuses have been used as animal models to study the regulation of fetal fluid balance. This study reports that the mid-gestation ovine fetus (70 +/- 1 d of gestation; term = 145-150 d) is susceptible to the development of fetal abnormalities (excess allantoic fluid--hydrallantois, with or without hydrops and hydranencephaly), when blood vessels in the neck are cannulated. Cannulation of one carotid artery and one jugular vein, or cannulation of a single jugular vein resulted in 5 out of 12 fetuses having abnormalities 1 wk later. In contrast, six fetuses at 115 d of gestation that had both carotids and one jugular vein ligated cranially and cannulated, developed hydranencephaly but no hydrops or hydrallantois. In the mid-gestation fetus hydrallantois [760 +/- 140 mL (n = 5) versus 104 +/- 23 mL (n = 7 controls), p < 0.001] occurred without alterations in the plasma concentrations of ACTH, cortisol, atrial natriuretic peptide, or aldosterone, as well as without anemia. Although the causes of the fluid abnormalities were not resolved, it is important to note the developmental differences in vulnerability.