Diethylene glycol (DEG) and diethylene glycol monoethyl ether (DEGEE) were evaluated for reproductive toxicity in CD-1 mice using a continuous breeding protocol. Compounds were administered in the drinking water at 0, 0.35, 1.75, and 3.5% w/v (DEG) or 0, 0.25 1.25, and 2.5% w/v (DEGEE). Exposure of the breeding pairs to 3.5% DEG for 14 weeks produced statistically significant decreases in the number of litters per pair, live pups per litter, proportion of pups born alive, and live pup weight. There was also a significant increase in the cumulative days to litter and a significant decrease in the number of pairs producing the third, fourth, and fifth litters for the 3.5% DEG-exposed mice. A crossover mating trial of the F0 mice to determine the affected sex was inconclusive, but suggested that offspring development was compromised in females exposed to 3.5% DEG. Slight maternal (F0) toxicity was noted for the 3.5 DEG group (7% decrease in body weight). The F1 generation, at 3.5% DEG, had decreased body weights at birth and exhibited poor postnatal survival. At the intermediate dose of DEG, body weights of both sexes were depressed at weaning, at onset of mating, and at necropsy. However, no adverse effects on reproduction were observed. DEGEE had no effect on reproduction in the F0 or F1 generation mice despite a 34% decrease in cauda epididymal sperm motility in the F1 males at 2.5% DEGEE. Other signs of toxicity observed in these F1 mice included increased relative liver weights. These data indicate that DEG is a reproductive toxicant in Swiss mice affecting fertility and reproductive performance, albeit at high doses (equivalent to 6.1 g/kg/day). However, its monoethyl derivative, DEGEE, is without adverse effects on fertility and reproductive performance.