Interstitial lung disease frequently complicates rheumatic disorders, especially polymyositis-dermatomyositis, rheumatoid arthritis, systemic sclerosis, and mixed connective tissue disease. In this article, we review the current data supporting the use of azathioprine, cyclophosphamide, chlorambucil, cyclosporine, and methotrexate in the management of chronic interstitial pneumonitis-fibrosis. The literature addressing the utility of these immunosuppressive-cytotoxic agents, however, consists almost entirely of anecdotal successes and small, uncontrolled series. Although no convincing data have proven that the use of any of these agents with or without corticosteroids is superior to therapy with corticosteroids alone, the literature may suggest a slight long-term survival advantage when either azathioprine or cyclophosphamide is added to prednisone therapy. Studies in which cyclosporine was used, however, have been less encouraging. Data regarding the use of chlorambucil and methotrexate are too sparse to permit any conclusions. Further controlled studies are required to clarify the role of these immunosuppressive agents in the treatment of interstitial lung disease.