We examined the question of what distinguishes persons with musculoskeletal disease who continue working after onset of illness from those who do not. We also investigated why persons with musculoskeletal disease have high rates of work disability relative to those with other chronic conditions of comparable activity limitation. Data regarding 3,100 persons with limitations in activities and chronic disease who were respondents to the 1978 Social Security Administration Survey of Disabled and Non-Disabled Adults were used. Persons with musculoskeletal disease who stopped working had poorer overall health status and physical function, and different work attitudes and working conditions than did those who continued to work. Symptoms of the musculoskeletal condition were poor predictors of whether work disability would result. Persons with musculoskeletal conditions had high rates of work disability, relative to those with other chronic conditions, primarily because of their age, level of comorbidity, and the interaction of the physical limitations imposed by their illness and the requirements of their jobs. They had similar levels of commitment to work and a similar proclivity to seek alternative sources of income as did those with other chronic diseases.