OBJECTIVE To determine effects of intra-articularly administered 6alpha-methylprednisolone acetate (MPA) in exercised horses with carpal osteochondral fragmentation. METHODS 18 horses: 3 groups of 6 each. METHODS An osteochondral (chip) fragment was created in 1 randomly chosen middle carpal joint of each horse. Polyionic fluid (PF) was injected into both middle carpal joints of horses in the control group. In horses of the MPA-control group, MPA was injected into the middle carpal joint without an osteochondral fragment; a similar volume of PF was injected into the contralateral middle carpal joint. In the MPA-treated group of horses, 100 mg of MPA was injected into the middle carpal joint containing the osteochondral fragment; a similar volume of PF was injected into the contralateral joint. Injections were administered on postsurgical days 14 and 28, and horses were exercised on a high-speed treadmill for 8 weeks, starting on postsurgical day 15. RESULTS Clinical improvement in degree of lameness was not associated with MPA administration. Joints that contained an osteochondral fragment and were treated with MPA had lower prostaglandin E2 concentration in synovial fluid, and lower scores for intimal hyperplasia and vascularity in synovial membrane, compared with PF-treated joints. However, articular cartilage erosion and morphologic lesions suggested possible deleterious effect of intra-articular MPA administration. CONCLUSIONS Some beneficial effects of MPA administration on synovial fluid and synovial membrane were identified; however, the deleterious findings contrast with those associated with triamcinolone acetonide used in a similar model, but agree with other results of MPA administration in normal and abnormal joints.