Intradermal tests with purified nuclear antigens from calf thymus nucleoprotein, histone, and deoxyribonucleic acid were carried out on 258 patients with various rheumatic and nonrheumatic diseases and on 46 healthy controls. A wide spectrum of variation in the degree of reactivity of the different patient populations studied was noted. At 24 hours postinjection, most of the patients with systemic lupus erythematosus (SLE) showed strong reactions (induration, 10 mm or more) to histone and nucleoprotein, and 40% of them to DNA. On the other hand, most of the patients with other diseases exhibited weak (induration, 0 to 4 mm) or intermediate (induration, 5 to 9 mm) reactions to the nuclear antigens. The study suggests that, when proper interpretive criteria are applied, the greater skin reactivity to purified nuclear antigens from calf thymus observed in patients with SLE may serve as another useful criterion to aid in distinguishing SLE from other diseases.