Most but not all Lyme disease patients produce specific IgE antibodies to Borrelia burgdorferi. Development of IgE antibodies paralleled that of other immunologic classes and appeared to be directed against a polypeptide with a molecular weight of 41,000. Total serum IgE levels in Lyme disease patients were usually within the normal range in all stages of the disease. However, highly elevated total serum IgE in certain patients were not correlated to any particular disease stage nor to specific antibody titers. Spirochetes and spirochetal sonicates in high concentration induced release of histamine from basophils derived from both patients and controls. At lower antigen concentrations, histamine release could be induced only from basophils derived from patients. Synovial fluids from patients with Lyme arthritis contained IgE but only negligible amounts of histamine.