The primary objective of the present study was to compare the rates of plasma clearance and hepatic utilization of stearic (18:0), myristic (14:0) and linoleic (18:2) acids, as introduced via chylomicrons. Lymph chylomicrons were specifically labeled in vivo with [14C]stearic and (SA), [14C]myristic acid (MA), or [14C]linoleic acid (LA) by infusing donor rats intraduodenally with the labeled fatty acids in a lipid emulsion. Following intravenous injection of recipient rats with the labeled chylomicrons, the rates of plasma clearance and incorporation of the label in triglycerides (TG), phospholipids (PL) and other lipids in the liver were compared at 5, 15 and 30 min. [14C]SA was cleared at a slightly faster rate (t1/2=7.0 min) than [14C]MA (t1/2=8.1 min) and [14C]LA (t1/2=8.0 min) (P<0.05). [14C]SA was accumulated in the liver at a significantly faster rate than [14C]MA and [14C]LA. At the peak (15 min) of hepatic uptake, 30.3% of [14C]SA, 26.2% of [14C]LA and 21.9% of [14C]MA were recovered in the liver. At 30 min, 33.5% of [14C]SA was taken up by the liver, whereas 27.8% of [14C]LA and only 15.2% of [14C]MA were removed. In the liver, the percentage of [14C]SA incorporated into PL steadily increased with time, whereas the percent-age incorporated into TG decreased. [14C]SA was preferentially incorporated into PL at all time intervals, as compared with [14C]MA and [14C]LA. At 30 min, 38.6% of [14C]SA was found in PL, and only 5.2% of [14C]MA and 12.0% of [14C]LA were present in PL. A large proportion of hepatic [14C]MA remained unesterified (free fatty acid) throughout the 30-min period, with a small proportion incorporated into PL and TG. Of the total liver14C radioactivity recovered at 30 min, 63.8% of [14C]MA, 48.8% of [14C]LA and 25.5% of [14C]SA were found unesterified. During 30 min, a significantly greater amount of [14C]MA (76.9%) was oxidized in both the liver and the peripheral tissue combined, compared with [14C]LA (64.7%) and [14C]SA (61.2%). A higher proportion of [14C]LA was incorporated into TG than into PL at all time intervals. No differences were noted in the relative distribution of14C in cholesterol and other lipids among the three fatty acids. Using labeled fatty acids incorporated in vivo into chylomicrons, the present study demonstrated that SA, MA and LA are distinctly different in their metabolic behavior. During the initial 30 min after their entry into the blood, 92-95% of the fatty acids were cleared. During this early phase of metabolism, [14C]SA was preferentially utilized for liver PL synthesis, whereas [14C]LA was better incorporated into TG. [14C]MA was poorly incorporated into hepatic lipids, but was preferentially oxidized in the liver or utilized by the peripheral tissue.