Recent studies have linked maternal consumption of an unbalanced high-protein, low-carbohydrate diet in late pregnancy with raised adult blood pressure in the offspring. Because high-protein diets stimulate the hypothalamic-pituitary-adrenal axis, we hypothesized that an unbalanced maternal diet might increase maternal cortisol levels, exposing the fetus to excess cortisol and programming lifelong hypersecretion of cortisol. We therefore measured fasting plasma cortisol concentrations in 251 subjects, 28-30 yr old, whose mothers had been advised to eat 0.45 kg of red meat daily during pregnancy and avoid carbohydrate-rich foods. Cortisol concentrations were higher in subjects with lower body mass index (P < 0.0001) and in those who reported recent vigorous activity (P = 0.03) and greater alcohol consumption (P = 0.004). Allowing for gender, current body mass index, activity, and alcohol consumption, cortisol concentrations increased 5.4% per portion of maternal meat/fish consumption per day (P = 0.03), decreased 3.3% per portion of maternal green vegetable consumption per week (P = 0.14), and were 12.2% higher in those born into manual social class families (P = 0.03). The specific advice given to mothers in this study precludes direct application to other populations, but the findings provide the first human evidence that an unbalanced maternal diet during late pregnancy may program lifelong hypercortisolemia in the offspring.