The geographical and age distributions of endemic Burkitt's lymphoma (eBL), in Africa, parallel those of certain arboviruses, which include chikungunya fever. Increased incidences of antibodies to assorted arboviruses, including chikungunya, have been found in eBL sera compared to controls. An increased incidence and space-time case-clusters of eBL occurred during a chikungunya fever epidemic which were confirmed by serology and clinical observation. The present study, conducted in 1987-89, involved 108 eBL patients, and 97 local and 111 hospital controls. We examined, as hospital controls, patients with afebrile, non-malignant conditions admitted to Kamuzu Central Hospital, Malawi, during the eBL patients' first admission there. Analyses were for hospital controls and eBL patients at the end of their first admission and for local controls and eBL patients at the beginning of their third admission, about 8 weeks after the day of first admission, because of the local controls' temporal bias. Patients in case-clusters were among those seropositive for chikungunya virus, with a history compatible with arbovirus infection preceding the lymphoma, suggesting involvement of chikungunya virus in the case-clusters and a possible association between recent infection with this virus and development of the lymphoma. eBL patients were significantly more likely to be seropositive for chikungunya virus antibody (68x5%) than either hospital controls (46.8%) or local controls (50x5%) (P = 0x002 and 0x009, respectively), raising the possibility of an association between infection with an arbovirus and developing eBL in children already primed by holoendemic malaria and Epstein-Barr virus infection.