To characterize the clinical presentation and course of African tick-bite fever, a recently rediscovered rickettsiosis caused by Rickettsia africae (a new species within the spotted fever group of rickettsiae), to establish its relationship with Amblyomma tick species, and to discuss its role in the etiology of fever in patients who are returning from the tropics.Seven patients who returned from Zimbabwe of the Republic of South Africa and presented with fever.Cases were recognized clinically by the presence of multiple taches noire and were diagnosed as having a rickettsial infection by identification of the organisms in circulating endothelial cells. The causative role of R africae was further demonstrated using cross-absorption and immunoblotting of patients' serum samples and isolation of the agent from blood and skin biopsy specimens. Isolates were characterized using the restriction fragment length polymorphism-polymerase chain reaction and sequence analysis of the gene that encodes for the 190-kd Rickettsia-specific antigen.All 7 patients presented with fever and multiple taches noire. Further physical examination of patients revealed lymphadenopathy, lymphangitis, and edema, but there were virtually no signs of a rash. These findings are characteristic of R africae-infected patients and are distinct from those observed in patients with Rickettsia conorii-induced Mediterranean spotted fever. All 7 patients were infected with R africae as demonstrated by immunoblotting or isolation of the agent, and all were cured.With increasing international travel, a need for the recognition of rickettsial diseases by physicians is becoming more important. Tick-bite fever, a disease caused by R africae and transmitted by Amblyomma ticks, is characterized by multiple taches noire, lymphadenopathy, lymphangitis, and edema, but no rash or a discrete rash. It is a frequent but benign disease that physicians should consider when presented with febrile patients returning from southern Africa.