Aerobic capacity is a complex trait that defines the efficiency to use atmospheric oxygen as an electron acceptor in energy transfer. Copenhagen (COP) and DA inbred rat strains show a wide difference in a test for aerobic treadmill running and serve as contrasting genetic models for aerobic capacity. A genome scan was carried out on an F(2)(COP x DA) segregating population (n=224) to detect quantitative trait loci (QTLs) associated with aerobic running capacity. Linkage analysis revealed a significant QTL on chromosome 16 (lod score, 4.0). A suggestive linkage was found near the p-terminus of chromosome 3 (lod score, 2.2) with evidence of an interaction with another QTL on chromosome 16 (lod score, 2.9). All three QTLs showed a dominant mode of inheritance in which the presence of at least one DA allele was associated with a greater distance run. These results represent the first aerobic capacity QTLs identified in genetic models.