This study evaluated the relationship between leg strength and endurance run performance, independent of aerobic capacity (V̇O_2peak), body size, and gender, in children and adolescents with mild or moderate mental retardation. Twenty-six individuals (15 boys and 11 girls) volunteered and underwent tests of V̇O_2peak, isokinetic leg strength, and endurance run performance (600-yard ran/walk and 20-m shuttle run). Results showed that leg strength was significantly related to both types of run performance; however, when controlling for V̇O_2peak, body size, and gender, leg strength was a more significant contributor to the 600-yard run/walk than to 20-m shuttle run performance. Gender did not influence these relationships. These data suggest that leg strength has a significant influence on endurance run performance in children and adolescents with mild or moderate mental retardation.