Collagen arthritis in rats is an animal model of polyarthritis that can be produced by an intradermal injection of homologous or heterologous native type II collagen emulsified in incomplete Freund's adjuvant (ICFA) 1 (1). The disease, which resembles human rheumatoid arthritis in many aspects (2), is not completely understood but appears to be the result of an autoimmune response to type II collagen (3, 4). It has recently been reported that the development of arthritis and the immune response to type II collagen are suppressed by pretreating the rats with immunosuppressive agents such as cyclophosphamide, azathioprine, and steroids (5-7). Cyclosporin A (CS-A), a new antilymphocytic drug, has been described as a potent immunosuppressive agent. Several lines of evidence suggest that the action of CS-A is predominantly or exclusively limited to T cell-mediated immune responses (8-1 1). Its usefulness is currently being actively investigated in various in vivo and in vitro conditions, and great expectations have been placed on CSA because its remarkable immunosuppressive potency is associated with a very low degree of myelotoxicity (12). In the present study, we evaluated CS-A for its effectiveness in preventing the development of collagen arthritis by treating the rats for the first 14 d with CSA. In an attempt to gain further insight into the mode of action of CS-A, we also investigated the effects of CS-A treatment in three different regimens: (a) only during the induction phase of immunity; (b) only during the immediate preclinical phase of arthritis; (c) on the established disease. This report describes some preliminary results of CS-A in this animal model of polyarthritis.