A two-step approach for diagnosis of Lyme disease, consisting of an initial EIA followed by a confirmatory Western immunoblot, has been advised by the Centers for Disease Control and Prevention (CDC). However, these criteria do not examine the influence of the prior probability of Lyme disease in a given patient on the predictive value of the tests. By using Bayesian analysis, a mathematical algorithm is proposed that computes the probability that a given patient's Western blot result represents Lyme disease. Assuming prior probabilities of early Lyme disease of 1%-10%, the current CDC minimum criteria for IgM immunoblot interpretation yield posttest probabilities of 4%-32%. The value of the two-step approach for diagnosis of early Lyme disease may be limited in populations at lower risk of disease or when patients present with atypical signs and symptoms.