Two regulatory mechanisms, based on the contrasting concepts of imprinting (clonal theories and idiotypic networks) and of ongoing regulation of immune responses (by antigen and end products with specificity for antigen), give rise to different predictions and approaches to the question of autoimmunity and autoimmune disease. Both concepts have legitimacy. however, if a ranking in terms of explicative power must be given, ongoing regulation is more plausible since it accounts more fully for basic events in immune responses and in autoimmune phenomena. Many instructive findings have emerged from experiments based on this latter concept, furthermore, the approach has only received limited notice and, thus. has not yet been exhausted.