Human granulocytic ehrlichiosis (HGE) is a recently described rickettsiosis in the United States transmitted by Ixodes species ticks. In Europe, only a few studies on HGE exist. Two hundred Bulgarian patients with tick bites and 70 healthy blood donors were tested for HGE using an immunofluorescence assay with the HGE agent as an antigen. Elevated antibody titers (> or = 1:80) were found in 14 (9.7 %) of 145 patients with erythema migrans, two (8%) of 25 tick-exposed patients with lymphadenopathy only, one (20%) of five patients with tick bite with fever, chills, and headache, one (4%) of 25 healthy tick-exposed patients, and two (2.9%) of 70 blood donors. These results show for the first time that HGE is probably common in southeastern Europe. The study provides evidence of coinfection or concurrent infection of patients with Lyme disease and HGE, thus supporting the possible role of I. ricinus for transmitting the HGE agent.