This study estimated the total cost of musculoskeletal disorders for Canadians in 1994 and assessed the sensitivity of these cost estimates to variations in the definition of musculoskeletal disorders. Disease-related costs, from a societal perspective, were measured using a prevalence-based analysis. First, direct treatment costs, including expenditures on hospitals and other institutions, physicians and other health professionals, drugs, research, and other items were assessed. Second, indirect costs associated with lost (or foregone) productivity due to disability and premature mortality were evaluated using the human capital aroach. The total cost of musculoskeletal disorders in Canada was $25.6 billion (in 1994 Canadian dollars, $1.00 CDN approximately $0.75 US) or 3.4% of the gross domestic product. Direct and indirect costs were estimated at $7.5 billion and $18.1 billion, respectively. Lower and upper bound estimates of the total cost of musculoskeletal disorders, derived from the sensitivity analysis, were $19.9 billion and $30.8 billion, respectively. Wide variations were reported in the total cost of various musculoskeletal disorder subcategories, with the highest costs reported for injuries ($10.7 billion), back and spine disorders ($8.1 billion), and arthritis and rheumatism ($5.9 billion). The economic cost of musculoskeletal disorders was substantial and was sensitive to the definition of musculosketal disorders and other underlying assumptions. The hallmark of this study was the variation between subcategories in their cost, pattern of health resource use, and sequelae. The cost estimates may provide guidance in setting priorities for research and prevention activities.