The in vivo effects of corticosteroids on osteoarthritic (OA) lesions were examined in 12 dogs in which the anterior cruciate ligament had been sectioned. Six were treated with oral prednisone and 6 were treated with intraarticular (IA) injections of triamcinolone hexacetonide (TH), at surgery and 4 weeks later. Twelve other operated dogs received no treatment. All dogs were killed 8 weeks postsurgery. Four of 15 normal control dogs received IA TH injections. Operated untreated dogs developed significant cartilage lesions on the femoral condyles and tibial plateaus with prominent osteophytes. Operated dogs treated orally or with IA injections had a significant reduction in osteophyte size. Cartilage erosions on femoral condyles were observed in 25% of the untreated dogs, 8% of the dogs receiving oral prednisone, and none of the dogs receiving IA TH. In both groups of treated dogs, the size of the tibial plateau lesions was significantly reduced compared with the operated untreated dogs. Histologically, corticosteroids significantly reduced the severity of OA structural changes of the cartilage on both medial and lateral femoral condyles and tibial plateaus in operated animals, with the exception of the lateral plateaus of those treated orally. In electron microscopy studies, we found no evidence of increased cell degeneration or death associated with steroids. IA corticosteroids had no deleterious effects on normal articular cartilage. These results indicate that glucocorticoids administered orally or intraarticularly are effective against the development of OA lesions in this model.