Alterations in some aspects of immunologic reactivity in a group of patients with leprosy were found primarily in patients with the lepromatous form of the disease. Such patients had impaired lymphocyte transformation to streptolysin 0 antigen. The ability to form circulating antibodies was preserved. Levels of IgG and IgA immunoglobulins were increased in lepromatous disease while IgM levels were normal in all groups. The concentration of serum complement was normal in all patients with uncomplicated disease but was elevated in those lepromaotus patients suffering erythema nodosum leprosum (ENL) reactions or amyloidosis. Reticuloendothelial system phagocytic function was increased in patients with lepromatous leprosy and especially in those with ENL reactions. Thus, the lepromatous form of leprosy is associated with a variety of abnormal immunologic responses.