Many studies have documented that placental development is altered by a variety of environmental factors which alter placental bed blood flow and/or oxygen delivery. One of these is sustained weight-bearing exercise. The purpose of this investigation was to examine the effects of running throughout pregnancy on villous vascular development and cell proliferation by testing the null hypothesis that continuing a regular running regimen throughout pregnancy has no effect on villous vascular volume or cell proliferation at term. Accordingly, placentae of 11 healthy runners with uncomplicated pregnancies were matched by placental weight, maternal diet and birth weight with those of 11 healthy controls and examined using systematic random sampling and point counting of placental tissues stained immunohistochemically with either an endothelial (CD 31, PECAM-1, endoCam) or a proliferative (Ki-67, MIB-1) marker. The placentae of the runners had greater villous vascular volumes in both absolute (77 +/- 20 cm(3) versus 47 +/- 18 cm(3), p < 0.02) and relative (% of total villous volume: 29 +/- 5% versus 20 +/- 6%, p < 0.003) terms. Likewise, they had a greater proliferation index (45 +/- 14 mitoses/1000 nuclei versus 29 +/- 10 mitoses/1000 nuclei, p < 0.008). We conclude that continuing to run regularly throughout pregnancy increases both absolute and relative villous vascular volume and cell proliferation at term. We also speculate that this exercise effect may have clinical value in cases at risk for anomalous feto-placental growth as increased villous vascular volume should improve feto-placental growth by enhancing placental transfer of oxygen and diffusible substrate.