Maternal hypoxemia has been associated with fetal-growth retardation and placental hypertrophy. Here, rats were exposed to carbon monoxide (CO), 100 ppm, at different stages of gestation to determine when during pregnancy placental hypertrophy can be elicited, whether hypertrophy is sustained when the stimulus is removed, and whether placental hypertrophy correlates with maintenance of normal fetal growth. Groups of rats (11-17 per group) were exposed to CO, throughout gestation, or over days 1-16, 4-12, 10-22 and 18-22, to cover significant periods of placental growth. Maternal carboxyhemoglobin levels were estimated to be in the order of 10-14%, but there was no effect on fetal survival. Fetal weights were significantly reduced by 8 and 6% in groups treated over days 1-22 and 10-22 of pregnancy, but not in those where treatment ceased before term, and surprisingly not in the group treated over days 18-22, the stage of maximal fetal growth. Placental weights were significantly increased by 11-13% in all groups in which carbon monoxide exposure was continued to term, but were unaffected in cases where treatment ceased before term. These results show that near term the placenta, when it is thought to normally reach the limit of its functional capacity, can hypertrophy in response to CO, and suggest that this response benefits the fetus presumably by improving oxygen transport.