Objective: Recent genetic studies indicate that Drosophila melanogaster could be a powerful model to identify genes involved in mammalian adipocyte differentiation and fat storage. The objective of our study was to identify quantitative trait loci (QTLs) that contribute to variation in triacylglycerol (TAG) storage in two D. melanogaster laboratory strains. Research Methods and Procedures: We used two genetic mapping procedures to identify loci with main and epistatic effects on TAG storage. First, using 68 recombinant inbred lines derived from the unrelated Oregon R and Russian 2b strains, we mapped the location of QTLs affecting TAG storage using both composite interval mapping and Bayesian epistatic methods. Second, we used the quantitative deficiency mapping procedure to identify candidate genes affecting this trait within one of the QTLs identified on the second chromosome. For both mapping experiments, flies were cultured in standard conditions. TAG content of 4- to 5-day-old flies, adjusted for live body mass and total proteins, was used as the phenotypic measure. Results. Multiple QTLs associated with variation in TAG storage were identified by the genome-wide recombination mapping method, and some of them were sex-specific. The QTLs had main effects, hut a male-specific epistatic interaction between two QTLs was also found. Finally, two closely linked QTLs were detected by deficiency mapping at 57E1-57E3 and 57E4-57F1 on chromosome 2, the first of which causes female-specific variation in TAG between the Oregon R and 2b strains. Discussion: Our results suggest that variation in TAG storage in D. melanogaster is controlled by different genetic mechanisms and different sets of QTLs in male and female flies. Copyright © 2005 NAASO.