The research objectives of this study were to evaluate the effects of osteopathic manipulative treatment (OMT) combined with maximal-effort exercise (MEE) on strength, coordination, endurance, and fatigue in female patients with multiple sclerosis (MS). Seven female subjects with MS participated in the 12-week study, which included intervention with OMT and MEE twice per week. Standardized tests for progression of MS and fatigue were used. Strength (maximal effort and impulse) was measured with the IsoPump exercise machine (IsoPump USA, Cleveland, Miss) during the three phases of the exercise protocol. Significant changes occurred in all but one measure of strength and on the 25-foot walk (P < .05), but not on the block-and-box test. The change in fatigue scores was not significantly different. Findings indicate that OMT combined with MEE significantly increases strength and ambulatory levels while not increasing fatigue in female patients with MS who have low to medium impairment. Qualitative data show that this intervention also produces beneficial effects in activities of daily living.