Replacement of dietary fat with carbohydrate may not reduce the overall risk of coronary heart disease (CHD), because this elevates plasma triacylglycerol (TAG) concentrations. The lipoproteinemic effects of a high-carbohydrate diet are likely to be more marked shortly after the initiation of such a diet than after longer periods of intervention during which adaptive processes may counteract the initial effects. Therefore, we studied the postprandial responses to a standard meal after 3-day dietary intervention periods. An additional objective was to establish a model for future study of the mechanisms involved. Nine normolipidemic men consumed the meal (1.2 g fat, 1.1 g carbohydrate, and 0.2 g protein per 1 kg body mass) after 3 days on a high-carbohydrate diet (68% +/- 3% energy from carbohydrate, mean +/- SD) and also after 3 days on an isoenergetic high-fat diet (66% +/- 5% energy). Venous blood samples were obtained from fasted subjects and for 6 hours after the meal. In the fasted state, TAG was higher after the high-carbohydrate diet (1.18 +/- 0.18 v0.62 +/- 0.09 mmol/L, mean +/- SEM, P = .02) and high-density lipoprotein (HDL) cholesterol was lower (1.01 +/- 0.08 v 1.10 +/- 0.09 mmol/L, P = .002). The area under the plasma TAG concentration versus time curve was 42% +/- 7% higher after the high-carbohydrate diet (P = .003). After the high-carbohydrate diet, the postprandial insulin response did not differ between trials, but glucose and 3-hydroxybutyrate responses were lower (P = .009 and P = .02, respectively) and the lactate response was higher (P = .001). Plasma nonesterified fatty acids (NEFAs) were lower after the high-carbohydrate diet in the fasted state and for 4 hours postprandially, but were higher thereafter (interaction of time x trial, P = .001). These results indicate that compared with a high-fat diet, the plasma TAG response to a standard high-fat meal is markedly higher after a few days on a high-carbohydrate diet, with major differences in the associated metabolic milieu. The magnitude of these changes and the rapidity with which they developed suggest that this model may be attractive for future studies of the underlying mechanisms.