Autoantibody determinations are frequently used by rheumatologists to establish the diagnosis or assess follow up clinical status in patients with connective tissue diseases. Such autoantibodies are often presumed to have harmful effects, particularly since some such as anti-native DNA or anti-Ro have frequently been related to tissue damage or to functional impairments. However, there are many other autoantibodies which react with antigenic components of normal autologous tissues which have not been demonstrated to have self-damaging or harmful effects. Some of these autoantibodies may actually represent natural built-in mechanisms of feed-back inhibition, serving to modulate normal physiologic function. Autoantibodies may be compared to chameleons since their function or quality is often judged by the company they keep or by their anatomical localization. Since many autoantibodies to intra-cellular products seem to react with active sites of important biologic molecules, they may provide us with a much sharper image of a number of natural cellular functions.