In rats, protein deprivation during pregnancy alters hepatic glucose handling in the adult offspring, in part by changing the activity of key enzymes involved in glucose metabolism (1). Our preliminary data suggest that these changes arise in utero in response to undernutrition (2). Since responsiveness of the hepatic glucogenic pathway to undernutrition increases towards term in fetal sheep (3), this study examined the effect of feeding rats a low protein (LP) diet for different periods of pregnancy on fetal hepatic activities of the rate-limiting glucogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphenolpyruvate carboxykinase (PEPCK). After mating (0 days), female Wistar rats were fed ad libitum either normal chow (20% protein, n=6) or a low protein diet (8% protein) for set periods from 0-10 days (n=6), 10-20 days (n=7), or 0-20 days (n=6). On day 20 (term 21 days), the fetuses were delivered for tissue collection under terminal anaesthesia. Fetuses and placentae were weighed and fetal livers frozen in liquid nitrogen for determination of G6Pase and PEPCK activities (4). Data are presented as mean (± SE) of litter means for each animal. Maternal protein deprivation from 0-10 days of pregnancy had no significant effect on fetal or placental weights, or on hepatic G6Pase and PEPCK activities (Table 1). In contrast, fetuses of mothers fed LP from 10-20 days or 0-20 days had lower body weights and higher G6Pase and PEPCK activities than controls (Table 1). Neither hepatic protein content nor litter size varied significantly with dietary treatment. These results show that undernutrition during the second half of gestation increases hepatic G6Pase and PEPCK activities in the fetal rat. This suggests that the critical period for prenatal nutritional programming of hepatic glucose metabolism may be the last 10 days of gestation in the rat.