A 48-h fast extends the estrous cycle of virgin rats and, when instituted on days 13 and 14 postpartum (pp), prolongs lactational infertility. We investigated the ability of 2-deoxy-D-glucose (2DG) alone or combined with mercaptoacetate (MA) to mimic these effects of fasting. In Experiment 1, we monitored estrous cyclicity in virgin rats receiving 800, 1200, or 1600 mg/kg/day of 2DG during metestrus and diestrus. In Experiment 2, we assessed the effects of 2DG (1600 mg/kg/day) given on days 13 and 14 pp, on the duration of lactational infertility. In Experiment 3, the combined effects of 2DG (1600, 2000, or 2400 mg/kg/day) and MA (180 mg/kg/day) on the length of lactational diestrus were evaluated. 2DG was sufficient to extend the estrous cycle of virgin rats, but neither 2DG alone nor given with MA prolonged the length of lactational diestrus. Results suggest that lactating rats are less sensitive than virgin rats to the effects of metabolic fuel inhibition on fertility. These data are discussed in relation to the hormonal state of the dam as well as in relation to the effects of these drugs on lactational performance.