Evidence of a gene-exercise interaction for traits related to body composition is limited. Here, the association between the lipoprotein lipase (LPL) S447X polymorphism and changes in body mass index, fat mass, percent body fat, abdominal visceral fat measured by computed tomography, and post-heparin plasma LPL activity in response to 20 wk of endurance training was investigated in 741 adult white and black subjects. Changes were compared between carriers and noncarriers of the X447 allele after adjustment for the effects of age and pretraining values. No evidence of association was observed in men. However, white women carrying the X447 allele exhibited greater reductions of body mass index (P = 0.01), fat mass (P = 0.01), and percent body fat (P = 0.03); in black women, the carriers exhibited a greater reduction of abdominal visceral fat (P = 0.05) and a greater increase in post-heparin LPL activity (P = 0.02). These results suggest that the LPL S447X polymorphism influences the training-induced changes in body fat and post-heparin LPL activity in women but not in men.