Unilateral medial meniscectomy was performed on two groups of sheep. At 1 week post-operatively, one group (N = 5) underwent a regimen of moderate walking exercise (24 km/week), while the other group (N = 5) received no exercise. Two groups (N = 6 and 8) of unoperated sheep were used as exercised and unexercised controls for the respective meniscectomized groups. Six months post-surgery all groups were sacrificed and their knee joints were examined macroscopically using established scoring systems. In both groups, meniscectomy induced cartilage and bone changes typical of early hypertrophic osteoarthritis. However, meniscectomized animals subjected to the exercise program developed more severe cartilage lesions and osteophytes than their unexercised counterparts. While the cell density in femoral cartilage of the meniscectomized and exercised group was similar to controls, that of the meniscectomized but unexercised animals was higher. We conclude form these data that in this animal model exercise exacerbated the lesions induced in articular cartilage by meniscectomy.