We have determined the primary structure of human liver fatty acid binding protein from an analysis of a full length cDNA. This 127-residue 14,178-Da protein exhibits a high degree of sequence conservation when compared to its orthologous homologue, rat liver fatty acid binding protein. It appears likely that this polypeptide arose from two intragenic duplication events. Using a variety of computational techniques, we were unable to find any evidence of amphipathic alpha helical domains in this protein nor any sequence similarities to apolipoproteins and serum albumins. A family of paralogous proteins was defined, whose members share a remarkable degree of sequence homology with share a remarkable degree of sequence homology with human liver fatty acid binding protein. These include rat intestinal fatty acid binding protein, the cellular the P2 protein of myelin. It appears that the small cytosolic fatty acid binding proteins have evolved structural features necessary for lipid-protein interaction which are different from those present in some familiar and better studied extracellular sequences.