The CD4 and CD8 glycoproteins which predominantly exist on T-helper and T-suppressor/cytotoxic cells are the physiological ligands for major histocompatibility complex class I or class II molecules on target cells such as B cells and antigen-presenting cells. These CD4 and CD8 molecules occur not only bound to membranes but also in soluble form in the serum. They may deliver regulatory signals to immunocompetent cells in vivo. The recent development of a solid-phase immunosorbent assay for soluble CD4 and CD8 molecules has enabled us to gain insight into the etiopathogenesis of autoimmune diseases on the basis of T-cell functional disability. This paper discusses the pathogenesis of autoimmune rheumatic diseases based on the findings for these molecules.