The need for protein-mediated transport of long-chain fatty acids into the cell is hotly debated, and the reviews make interesting reading (eg, refs. 4–9). One line of argument is that the rates of flip-flop of free fatty acids across lipid bilayers are sufficiently fast that protein transfer mechanisms are not required to explain physiological uptake (7, 8). On the other hand, there is evidence that several proteins facilitate long-chain fatty acid uptake (eg, ref. 6). There is also evidence of saturability of fatty acid uptake and of competitive inhibition, which would appear to suggest that specific fatty acid receptors or transporters are involved. The counter argument is that these findings may be explained by physical limits to the uptake process related to the partitioning of fatty acids between albumin and the cell membranes (8). Proponents of the fatty acid transport systems concede that simple diffusion may account for a portion of the observed rates of fatty acid uptake (4, 5). It is also agreed that this may become the major mechanism if cells are suddenly flooded with high micromolar concentrations of fatty acids, as could occur under experimental conditions. The proponents of passive diffusion seem prepared to give less ground at this stage, noting that passive transfer is fast enough to account for observed rates of fatty acid uptake, and going so far as to challenge that “these observations... make it difficult to imagine why nature would use resources for a purpose not needed”(8). Transport of long-chain fatty acid definitely does occur in Escherichia coli, where it is tightly linked to CoA-esterification via the acyl CoA synthetase (10). In mammalian and yeast cells, it appears that the acyl CoA synthetase merely enhances uptake indirectly. Formation of the polar CoA ester effectively traps the fatty acid in the cell and thus functions as part of a facilitated diffusion process. One of the CoA synthetases (ligases) is specific for arachidonic acid and other C20 fatty acids, although there is no evidence of its specific involvement in uptake (11). The membrane proteins implicated in fatty acid uptake in mammalian cells include FAT/CD36 (fatty acid translocase), FATP (fatty acid transport protein) and FABPpm (fatty acid binding protein-plasma membrane)(6). Two of these proteins (FAT and FABPpm) have separate and well-characterized functions, and FATP has homology to long-chain fatty acid CoA synthetase. FAT is homologous to CD36, a lipoprotein receptor and mediator of platelet aggregation and adhesion (12). FABPpm is a 40 kDa protein with ubiquitous expression that is identical in sequence to mitochondrial aspartate aminotransferase. There is clear evidence, nonetheless, that FABPpm is localized to the plasma membrane and increases fatty acid uptake when expressed in 3T3 fibroblasts (13). It is relevant to note that the vast literature on the binding and uptake of long-chain fatty acids is dom-