Low plasma levels of high-density lipoprotein (HDL) and apolipoprotein (apo) A-I often accompany human hypertriglyceridemia. In an animal model of hypertriglyceridemia, the lipoprotein lipase (LPL)-inhibited cynomolgus monkey, we reported that plasma levels of apo A-I were decreased and the fractional catabolic rate (FCR) of HDL apo was increased. To explore whether hypertriglyceridemia alone would alter plasma apo A-I levels and catabolism, hypertriglyceridemia was produced by intravenous (IV) infusion of 20% Intralipid into female cynomolgus monkeys. Baseline plasma triglyceride (TG) levels averaged 106 mg/dL. With infusion of 200 mg/kg/h Intralipid TG, plasma TG levels peaked at 967 mg/dL (range, 413 to 1,069; n = 6). More prolonged or more severe hypertriglyceridemia caused serious complications in several monkeys. Despite the severe hypertriglyceridemia, HDL TG content, HDL apoproteins, and plasma apo A-I levels did not markedly change, suggesting that very little HDL remodeling had occurred. Kinetic studies of HDL protein and apo A-I were performed in four pairs of monkeys. The two tracers were removed from the plasma at identical rates. In five pairs of animals, apo A-I turnover during control and Intralipid-induced hypertriglyceridemia was not significantly different. We hypothesize that apo A-I FCR is a function of HDL composition. Because Intralipid infusion did not alter HDL composition to the same degree as did LPL inhibition, its effects on HDL apo catabolism were not apparent.