Hematogenous dissemination has long been considered an important pathogenetic event in Lyme borreliosis but has been hard to document and characterize due to insensitive blood culture methods. In a series of recent investigations involving adult patients from the United States with erythema migrans, it was concluded that plasma was a better source of culture material than serum or whole blood, and yield correlated directly with the volume of material cultured. The rate of recovery of Borrelia burgdorferi from 9 mL of plasma exceeded 40%. Both the genotype of the strain of B. burgdorferi introduced by the tick and host factors, such as having a first episode of Lyme borreliosis and being more than 55 years of age, appear to affect the risk of hematogenous dissemination. Although the majority of spirochetemic patients are symptomatic, spirochetemia can be a subclinical event. In summary, hematogenous dissemination is a common and important feature of early Lyme borreliosis in the United States. The high rate, early onset and prolonged duration of risk of spirochetemia probably explain why untreated patients with erythema migrans may develop objective clinical manifestations at a distant anatomic site.