The antibody responses to the three genomic groups of Borrelia burgdorferi (B. burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii) were determined in 97 German patients with various manifestations of Lyme borreliosis. The geometric mean antibody titers in each patient group, determined by ELISA, were similar with each antigen preparation. By Western blotting, however, patients with meningopolyneuritis tended to respond to more spirochetal polypeptides of B. garinii, the group 2 strain, whereas those with arthritis recognized more antigens of B. afzelii, the group 3 strain (P < .03), as did those with acrodermatitis. Only 1 patient each with erythema migrans, arthritis, or acrodermatitis had weak reactivity with outer surface protein A (OspA), and none responded to OspB. It is concluded that differences among the three groups of B. burgdorferi may result in variations in the antibody response in European Lyme borreliosis.