The effects of either chronic exercise or chronic environmental hypoxia on placental CO diffusing capacity (DPCO) were examined in guinea pigs. Hartley guinea pigs with dated pregnancies were exercised moderately on a treadmill (10 m/min at an 8% grade for 15 min twice a day) or were exposed to hypoxia (12% O2) throughout the course of gestation. DpCO, fetal body, heart and brain wt, placental wt, and maternal body and heart wt near term (62-64 days) were measured. All parameters were compared to a control group of pregnant guinea pigs. Exercise at this level produced no changes in fetal body, organ or placental wt. Hypoxia caused a reduction in fetal body and brain wt and an increase in the ratio of brain, heart and placenta wt to body wt. DpCO in the exercise group decreased 34% to 2.16 .+-. 0.11 ml/(min .cntdot. Torr .cntdot. kg fetal wt) from a control value of 3.27 .+-. 0.10 ml/(min .cntdot. Torr .cntdot. kg). In the hypoxic group DpCO increased 63% to 5.33 .+-. 0.14 ml/(min .cntdot. Torr .cntdot. kg). Placental microsomal cytochrome P-450 concentrations were low in control animals and did not increase with hypoxia. Cytochrome P-450 apparently played no role in the increased placental DPCO with hypoxia.