Current hypotheses regarding the pathophysiology of rheumatic disease are depicted in Figure 1. Susceptible individuals, when exposed to microorganisms and/or drugs, can start the events depicted in Figure 1; the ability of the individual to respond to these exogenous agents is influenced by genetic factors including inherited deficiencies of the host's immune defense mechanisms. Microorganisms may then infect and/or effect mononuclear cells with persistence, or may be activated by environmental factors including UV light or other infections. If cell lysis results, antibodies can then be made to the cell (lymphocytotoxic antibodies) or cell products (ANA, etc.). The antibodies-to-lymphocyte membranes may interfere with lymphocyte function in a number of ways, including immunosuppression, and may also cause reactivation of this cycle. The antibodies may combine with antigens to form immune complexes that can be efficiently cleared by macrophages, have a feedback role in lymphocyte regulation, or in susceptible individuals deposit in tissue with subsequent inflammation. All or some of these steps or pathways may be under the influence of genetic factors.