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 post-weaning. All comparisons were made to strain and gender matched controls. Male DR-B6 offspring initially grew slower than controls; however, by 77d and 182d they were significantly heavier (p<0.05). Further, they had an increase %Fat mass (+70%, p<0.01) by 182d and were glucose intolerant at both 80d (p<0.001) and 186d (p<0.05). In contrast, weight, %Fat mass and glucose tolerance in DR-A/J males during postnatal life was not different from controls. Female DR-B6 mice showed catch-up growth during the first 77d of life; however, their weight, %Fat mass and glucose tolerance was not different from controls at 80d and 186d. Although female DR-A/J were heavier than controls at 182d (p<0.05), their %fat mass and glucose tolerance was not different from controls at 182d and 186d. The observed strain and gender differences offer a unique opportunity to begin to define gene-environment interactions that contribute to developmental origins of health and disease.