The ability of fatty acyl-CoA's and fatty acylcarnitines to penetrate phospholipid monolayers was comparatively studied, in view of the important role of both kinds of derivatives in fatty acid transport across mitochondrial membranes. The interaction occurs predominantly through hydrophobic forces. Acylcarnitines penetrate phospholipid monolayers more strongly than acyl-CoAs; in addition the former show a positive cooperativity when they bind to the interface. These properties would facilitate membrane transfer of fatty acylcarnitines over that of their CoA homologues.