We investigated the effect of cyclosporine (CsA) on force generation in 15 boys with Duchenne muscular dystrophy (DMD) by obtaining monthly measures of tetanic force and maximum voluntary contraction (MVC) of both anterior tibial muscles. During 4 months of a natural history phase, both tetanic force and MVC declined significantly. During 8 weeks of CsA treatment (5 mg/kg/day), significantly increased tetanic force (25.8 +/- 6.6%) and MVC (13.6 +/- 4.0%) occurred within 2 weeks. The maximum mean increase during treatment was 35.2 +/- 5.9% (tetanic force) and 19.0 +/- 4.6% (MVC). Side effects from CsA, gastrointestinal and flu-like symptoms, were transient and self-limiting. Thus, as previously reported with prednisone, CsA increases muscular force generation in the anterior tibial muscles of DMD patients.