In various autoimmune diseases it appears that NK activity is impaired, and that this phenomenon is significant in disease development. Impairment of NK activity may be the result of two different mechanisms. In systemic autoimmune diseases, in which various target organs are involved (nonorgan-specific), the peripheral blood NK level is generally lower than normal. This most likely allows the expression of autoimmune phenomena such as B cell hyperactivity and polyclonal antibody production, as is seen in SLE, due to a defect in the termination of the immune response. In autoimmune diseases with more localized, organ-specific lesions one can detect increased NK activity at the target organ itself. In these instances, the cytotoxic characteristic of the NK cell is more prominent. This theory explains why both increased and decreased NK activity may be observed in autoimmune diseases. In some disorders in which decreased NK activity was suspected of being crucial, immunomodulators, known to increase NK activity, were administered. Yet it is still difficult to separate the NK activity from the effect of the remaining immune system.