The local response of 18 patients with active systemic lupus erythematosus to 0.1 ml of intradermally injected 0.1% polymerized calf thymus DNA and synthetic double-stranded polyinosinic-polycytidylic acid was studied. In 14 patients positive for DNA, 61 f 8% of the inflammatory cells in the subepidermis at 24 hours were acid alpha-naphthyl acetate esterase-positive T lymphocytes. A leukocytoclastic vasculitis was observed in the deeper dermis. Rheumatoid arthritis patients and acne patients had negative responses. These results indicated an abnormal cellular and humoral in vivo response by patients with systemic lupus to DNA. It is suggested that the epidermal Langerhans cells were responsible for the topographic dichotomy of the local DNA response. Test results were positive for polyinosinic-polycytidylic acid in 12 patients, for DNA in 14 patients, and for both in 9 patients. In the 9 patients with positive results for both tests, comparison of responses to each test indicated that the reaction intensity was dependent on the patient and not on the type of polynucleotide acid that was injected.