The objective of this study was to characterize offspring responses to maternal dietary restriction (DR) in two phylogenetically distant strains of mice: A/J and C57BL/6J (B6). Pregnant mice were fed 100% or 70% of ad libitum between 6.5 and 17.5 days (d) gestation. Offspring were fed 100% ad libitum postweaning. All comparisons were made to strain and sex matched controls. Male DR-B6 offspring initially grew slower than controls; however, by 77 d and 182 d they were significantly heavier (P<0.05). Further, they had an increase percentage fat mass (+70%, P<0.01) by 182 d and were glucose intolerant at both 80 d (P<0.001) and 186 d (P<0.05). In contrast, weight, %Fat mass and glucose tolerance in DR-A/J males during postnatal life were not different from controls. Female DR-B6 mice showed catch-up growth during the first 77 d of life; however, their weight, %Fat mass and glucose tolerance were not different from controls at 80 d and 186 d. Although female DR-A/J were heavier than controls at 182 d (P<0.05), their %Fat mass and glucose tolerance were not different from controls at 182 d and 186 d. The observed strain and sex differences offer a unique opportunity to begin to define gene-environment interactions that contribute to developmental origins of health and disease.