The inheritance of obesity has been analyzed in an intercross between the mouse strains AKR/J and C57L/J. Two novel obesity quantitative trait loci (QTLs) have been identified using the strategy of selective DNA pooling. One QTL affecting adiposity, Obq3, was mapped to a 39-cM segment near the middle of Chromosome 2, with a peak lod score (5.1) just distal to the D2Mit15 locus. The AKR/J Obq3 allele confers increased adiposity in a nearly additive manner, and males are more affected than females. A second obesity QTL (Obq4) maps to the centromeric end of Chromosome 17, with a lod score peak of 4.6 at D17Mit143. The obesity-conferring allele is contributed by C57L/J and acts in a recessive or an additive manner. Obq4 also has more influence in males and affects the inguinal fat depot differentially. Obq3 and Obq4 account for 7.0 and 6.1% of the phenotypic variance in adiposity (gender-merged data), respectively. The possible relationships between these QTLs and previously described obesity QTLs and candidate genes are discussed. The large number of different obesity QTLs that have been described in mice and the relatively small effects contributed by individual loci suggest considerable genetic complexity.