This prospective study evaluated regular physical activity and self-reported physician-diagnosed osteoarthritis of the knee and/or hip joints among 16,961 people, ages 20-87, examined at the Cooper Clinic between 1970 and 1995. Among those aged 50 years and older, osteoarthritis incidence was higher among women (7.0 per 1000 person-years) than among men (4.9 per 1000 person-years, P = 0.001), while among those under 50 years of age, osteoarthritis incidence was similar between men (2.6) and women (2.7). High levels of physical activity (running 20 or more miles per week) were associated with osteoarthritis among men under age 50 after controlling for body mass index, smoking, and use of alcohol or caffeine (hazard ratio = 2.4, 95% CI: 1.5, 3.9), while no relationship was suggested among women or older men. These findings support the conclusion that high levels of physical activity may be a risk factor for symptomatic osteoarthritis among men under age 50.