Oxygen supply is an important regulator of the fetal placental capillarization. To determine the effects of long-term hypoxia on the fetal placental vessel arrangement pregnant guinea pigs were kept under hypoxic conditions (12% O2 for 45 days). Vessel casts showed a significant difference in branching and orientation of the vessels between the controls and the hypoxic animals. The hypoxic group had a less orientated capillary bed with increased branching and coiling. By light- and transmission electron microscopical studies, there was a decreased diffusion distance, a decreased diameter of the fetal capillaries, and an increased number of capillary cross-sections. These results are consistent with the hypothesis that chronic hypoxia is responsible for increased branching and coiling of the capillaries resulting in a dense network of short and narrow capillaries in the placenta.