Adults with GH deficiency (GHD) report weakness and fatigability. The origin of such symptoms is still debated. This work aimed to clarify whether weakness and fatigability depend on impairment of skeletal muscle contractile capacity. Five males with childhood-onset GHD (age +/- SE, 29.6 +/- 1.9) and 13 age- and sex-matched controls were enrolled in the study. Quadriceps muscle cross-sectional area (CSA), strength, twitch characteristics, and fatigue index of voluntary and electrically evoked contractions were determined in vivo in all subjects. Fiber type distribution and CSA of identified types of skeletal fibers were determined on needle biopsy samples of the vastus lateralis muscle of all subjects. Fiber type distribution was assessed on the basis of myosin heavy chain (MHC) isoform composition determined by electrophoresis on polyacrylamide gels. Fiber CSA was determined on cross-cryosections of fiber bundles immunostained by monoclonal antibodies against MHC isoforms. Absolute values of strength and fiber CSA of quadriceps were significantly lower in patients affected by GHD than in controls. However, once strength and fiber CSA were normalized for quadriceps CSA and subject height, respectively, differences disappeared. No difference was found between GHD patients and controls for quadriceps muscle twitch characteristics, fatigue index, and fiber type distribution. The results reported here suggest that weakness and fatigability in childhood-onset GHD do not have a skeletal muscle origin.