Two patients received oral penicillin for erythema migrans disease (EMD) in 1973 and 1977. Five and seven years later, respectively, they developed EMD for a second time after being bitten by ticks. The first and second erythema migrans lesions appeared in different places. Tests of sera evaluated for antibodies to Borrelia burgdorferi before (in one case), during and after the second episode of EMD remained negative (patient 1) or yielded an at least four-fold rise of IgG antibody titers, but did not become positive (patient 2). These cases provide evidence that reinfection in EMD may occur without a significant elevation of specific antibody titers.