S erial changes in circulating triglyceride, free fatty acids (FFA), insulin, and glucose have been measured in human subjects fed sucrose as the sole source of calories for 2- or 3-day periods. The sucrose was given either during the day with overnight fasting (19 subjects) or as continual 3-hour meals during the day and night (seven subjects). Insulin was infused overnight in five additional subjects on the day-feeding regimen to determine the effect on triglyceride concentration.The concentration of triglyceride increased during the study in all subjects, but there was a clear diurnal pattern in the response which was present even in the continual feeding studies. The rise in triglyceride occurred mainly overnight, and during the day there was frequently a fall in the concentration. The overnight increase was significantly less when insulin was infused. There were also diurnal fluctuations in FFA and insulin in both daytime and continual feeding regimens. The plasma FFA, like triglyceride, rose during the night and fell during the day while the insulin rose during the day and fell overnight.Separate statistical analysis of the daytime and overnight changes revealed that the changes in triglyceride were significantly but negatively correlated with changes in insulin during both periods. The changes in triglyceride and FFA were positively correlated during the day but not significantly related during the night. The data show that when sucrose is eaten for 2 or 3 days, there is a general increase in triglyceride concentration upon which are superimposed major diurnal fluctuations in the concentrations of triglyceride, insulin, and FFA. It is suggested that the highly significant inverse relationship between changes in triglyceride and insulin may be mediated through an effect of insulin on triglyceride removal.