This article reviews the current knowledge of genetic factors conferring susceptibility to several major rheumatic disorders, in particular, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus erythematosus (SLE), and Sjögren's syndrome. Emphasis is given to major histocompatibility complex associations with these diseases, particularly rapidly evolving knowledge of class II HLA genes and disease-conferring "epitopes." Non-MHC-linked genes, such as T cell receptor and immunoglobulin genes, also may be involved.