To characterize the serological response in humans to human granulocytic eh
rlichiosis (HGE), we prospectively observed 152 patients for as long as 42
months. HGE was confirmed by detection of morulae in blood smears, polymera
se chain reaction, blood culture, or a combination of these tests for 94 pa
tients (62.3%), and 92 (97.8%) of the patients had specific serum antibodie
s thereafter. One hundred twenty-six (99.2%) of 127 patients tested at 1 mo
nth were seropositive (89 of 127 patients had seroconversion), and 150 (98.
7%) of the 152 patients had become seropositive by 6 months. Eleven patient
s (7.3%) remained seropositive at 42 months. Neither antibiotic therapy ini
tiated during the first week of illness nor preexisting immunosuppressive c
onditions abrogated a serological response. Indirect fluorescent antibody t
esting of acute-phase and convalescent-phase serum samples is a sensitive t
ool for laboratory confirmation of HGE.