The oral fat load tests (OFLT) used to study postprandial lipemia are generally conducted during the day. A nocturnal fat load test could be convenient and physiologically more appropriate. We have therefore compared the lipemic responses of 9 normolipidemic young men to OFLT given at 2200 h (nocturnal) and at 0700 h (diurnal). Triglyceride and retinyl palmitate concentrations were measured for 10 h. Peak plasma concentrations or areas under curves (AUC) for triglyceride after the diurnal and nocturnal tests were not significantly different [2.17 +/- 0.78 (diurnal) vs. 2.04 +/- 0.87 mmol/L (nocturnal) and 13.12 +/- 4.45 (diurnal) vs. 13.74 +/- 5.79 mmol/(L. h) (nocturnal)]. Peak plasma concentrations and AUC retinyl palmitate for the two tests were not different [1.71 +/- 0.69 (diurnal) vs. 1.42 +/- 0.66 mg/L (nocturnal) and 7.17 +/- 3.98 (diurnal) vs. 6.63 +/- 4.23 mg/(L. h) (nocturnal)]. The diurnal triglyceride peak occurred significantly earlier (4.3 +/- 1.2 h) than the nocturnal peak (5.8 +/- 1.7 h, P < 0.05). We have developed a model using only three sample time points to predict AUC [triglyceride at 0 h, triglyceride at average peak-time (4 h for diurnal and 6 h for nocturnal tests), and triglyceride at 10 h], thus reducing the number of blood samples. The predicted AUC was well correlated with the total AUC after nocturnal OFLT (r = 0.98, P < 0.0001). The nocturnal test appeared to be well tolerated by the subjects. The three-point simplified protocol may well be suitable for studies on large groups of subjects.