The purpose of this investigation was to examine the effects of Multiple Sclerosis (MS) on the structural and functional characteristics of skeletal muscle. More specifically, we analyzed the myosin heavy chain (MHC) and fiber type distribution of the vastus lateralis, measured single fiber cross sectional area (CSA), and determined the isokinetic and isotonic strength of the knee extensor muscles. Six sedentary subjects with MS (age: 44 ± 2 yrs) and six sedentary gender-matched controls (age: 46 ± 4) were evaluated. EachMS subject was rated on the Kurtzke's Expanded Disability Status Scale (EDSS) and performed an 8-meter walk test to determine gait speed. Furthermore, the spasticity of the knee extensors was evaluated in each MS subject and weekly energy expenditure was estimated using the Yale Physical Activity Survey. Concentric and eccentric isokinetic strength of the right knee extensors (left in one MS subject) was determined at 60 and 180°/sec and a bilateral isotonic one-repetition maximum (1-RM) was evaluated in eachsubject. Muscle biopsies were taken from the right vastus lateralis (left in one MS subject) and individual fibers were dissected from these samples. Fibers were submitted to SDSPAGE with silver staining to determine MHC expression. Densitometry was performed on MHC hybrid fibers to determine the degree of co-expression. An additional section ofthe biopsy was stained for mATPase activity and further analyzed for single fiber CSA and fiber type. The mean EDSS score for the MS subjects was 5.4 ± 0.6 (range 3.5-6.5) and MS patients were slower than controls (p < 0.05) on the walk-test. AshworthSpasticity Scores ranged from 0 - 2. No differences were noted in weekly energy expenditure. The controls were 45 and 56% stronger than the MS group at isokinetic concentric velocities of 60 and 180°/sec (p < 0.05), respectively. The isotonic 1-RM andthe eccentric isokinetic contractions were not different between the two groups. There were no differences noted in any of the MHC isoforms or percentage of hybrid fibers. Furthermore, mATPase fiber type distribution and single fiber CSA were not different between the groups. There was a greater proportion of MHC IIx dominant MHC IIa/IIx fibers in the MS groups (p < 0.05). Multiple Sclerosis appears to result in large strengthdeficits, when compared to healthy individuals. Based on our findings, these strength differences cannot be explained by alterations in MHC/fiber type expression or decreases in fiber CSA. / School of Physical Education