The isokinetic strength of the knee extensor muscles of both limbs, at the speed of 30 degrees/second, was evaluated in 25 children and adolescents with Down syndrome. Comparison with two control groups of 40 intellectually average individuals and 30 individuals with mental retardation of unknown origin showed that both children and adolescents with Down syndrome were weaker than were the control subjects. Moreover, by the age of 14 years, adolescents with Down syndrome failed to show the muscle strength increase that physiologically occurs by this age. Interlimb comparison of knee extensor muscles showed a strength dominance in the 44% of individuals with Down syndrome, with a prevalence for the left leg. In conclusion, our data suggest the presence of a dysfunction of the neuromuscular system both at the level of the pyramidal system and/or of the neuromuscular junction, possibly as an expression of premature ageing.