Recessive mutations at the rat fatty locus (fa, facp), which produce obesity, insulin resistance, and diabetes, provide useful experimental models for similar phenotypes in humans. The molecular pathogenesis of the metabolic phenotype in animals segregating for fa is unknown and difficult to study once the confounding metabolic effects of obesity are present. Although various experimental methods distinguish preobese from lean rats (phenotypic markers and molecular markers genetically linked to fatty), technical difficulties limit their utility. We report the identification of two (GT)n simple sequence repeats (SSRs) near the rat phosphoglucomutase gene (Pgm1) gene and two SSRs, (GA)n and (GT)n, near the rat complement component 8 beta gene (C8b). These SSRs map to an approximately 4-cM interval flanking the fatty locus on rat chromosome 5. Use of these molecular markers in combination offers an improved method for early assessment of gene dosage for fa and hence for studying the fundamental molecular physiology underlying the derangements of metabolism and behavior resulting from mutations in this gene.