A B S T R A C T There was a rapid net uptake of free fatty acid (FFA) by human platelets when long-chain FFA, bound to human serum albumin, were incubated with platelet suspensions. Results from experiments in which both palmitate and albumin were labeled indicated that the fatty acid dissociated from the protein during uptake. Much of the FFA taken up by the platelet in short-term incubations remained in unesterified form, i.e., it was recovered as platelet FFA. As the incubation continued, increasing amounts of FFA were oxidized to CO2 and incorporated into platelet lipid esters, particularly lecithin. Essentially all of the fatty acid that was incorporated into the platelet FFA fraction was released rapidly from the cells when they were exposed to a medium containing FFA-free albumin. The magnitude of uptake into the platelet FFA fraction was similiar at 00 and 370C. Likewise, the rate and magnitude of FFA release from the platelet were similar at 00 and 37°C. Therefore, it is likely that both FFA uptake and FFA release occur by energy-independent mechanisms. The major effect of increasing the FFA concentration of the incubation medium was increased fatty acid uptake into the platelet FFA fraction. Similar results occurred when platelets were incubated in human plasma containing increasing amounts of added palmitate. At a given extracellular FFA concentration, considerably more of the saturated fatty acids, palmitate and stearate, were taken up as platelet FFA (4,5). In contrast, more linoleate than stearate was incorporated into lipid esters in both of these cells (4, 5).Human platelets, like most other mammalian cells, take up and metabolize long-chain FFA (6-8). Palmitic acid has been employed in most studies of FFA metabolism in platelets (6, 7), and except for incorporated into phospholipids (8), little is known about the way in which the other commonly occurring long-chain fatty acids are utilized. This question is of particular relevance for platelets because it has been reported that saturated FFA are much more effective than unsaturated FFA in causing platelet aggregation (9, 10). Such effects may result from differences in the way that platelets take up or metabolize saturated and unsaturated FFA. In order to examine this point, we compared the utilization of palmitic, stearic, oleic, and linoleic acids by suspensions of human platelets. The major difference that we observed was the extent to which each of these fatty acids was incorporated in unesterified form by the platelet. in order to obtain the platelet pellet. After removing the plasma, the platelets were resuspended in a solution containing 0.123 M NaCl, 0.0045 M KCl, and 0.015 m Tris buffer adjusted to pH 7.4 with 1 N HCL. The platelet count of each suspension also was determined, and enough Trisbuffered salt solution was added so that 1 ml of the suspension contained 109 platelets. Microscopic examination of the platelet suspension revealed only trace contamination with other cellular components of the blood. White blood cells were the ...