Glucose kinetics were studied in a group of nonobese humans with endogenous hypertriglyceridemia before, during, and after an infusion of graded increments of glucagon. The tracer methods employed permitted glucose turnover to be quantitated under non-steady state conditions. The rates of glucose production, disappearance, and fractional disappearance were related to the range of glucagon and insulin levels in each individual. The findings in hypertriglyceridemics were compared with those in lean normals of the same relative body weight and the same extracellular fluid volume per kg, as reflected by their apparent glucose space. Glucose production and serum insulin were each positively correlated to plasma glucagon concentrations in both hypertriglyceridemics and normals. Thus, with respect to these parameters, the hypertriglyceridemics were not resistant to glucagon. During the glucagon infusion, the glucose concentration rose more in the hypertriglyceridemics than in the normals because of a reduced total rate of glucose disappearance in the hypertriglyceridemics. In the normals the fractional disappearance rate of glucose was positively related to serum levels of insulin, whereas in the hypertriglyceridemics it was lower than normal and did not change in relation to insulin concentration. This demonstrated that, at least with respect to glucose utilization, lean hypertriglyceridemics can be resistant to insulin even in the absence of obesity.