Twenty-one patients with fixed drug eruption were studied with the lymphocyte transformation test. In no patient was there blast transformation when the responsible drug (1:10,000 dilution) was added to the lymphocyte culture. The addition to the lymphocyte culture of 0.4 ml of autologous serum, taken at the acme of the clinical reaction, produced blast transformation of the lymphocytes, and when the responsible drug (1:10,000 dilution) was added to this system, blast transformation increased by several times. The addition of the responsible drug to autologous serum obtained during clinical remission produced a minimal or negative response. These findings suggest that during fixed drug eruptions a blast transforming factor appears temporarily in the serum and increases its activity in the presence of the responsible drug. This factor spontaneously diminishes or disappears a few days after clinical exacerbation. (N Engl J Med 292:819–821, 1975). THE skin is frequently involved in drug reactions due to any administered therapeutic agent. In 1894, Brocq isolated and described a particular group from the various clinical pictures of cutaneous drug reactions that he called “fixed drug eruptions.” The clinical characteristics included a sudden onset of sharply circumscribed inflammatory patches, often urticated or bullous, reappearance in previously similarly involved hyperpigmented areas, and occurrence after both oral and parenteral readministration of the drug. Spontaneous resolution occurred within a few days, leaving the skin heavily pigmented in the affected area. The development of additional lesions in new areas with each provocation was. © 1975, Massachusetts Medical Society. All rights reserved.