Numerous sera from African patients with Burkitt's lymphomas (BL) or other malignant and nonmalignant diseases, as well as sera from various control populations, were titrated in indirect immuno-fluorescence tests for antibodies to the Epstein-Barr virus (EBV). The results reaffirmed the unusual frequency (87%) of high liters (≧1:160) among active BL patients. Although low titers (≦1:80) were found in some histologically confirmed cases, they were somewhat more frequent among a) patients whose diagnosis could not be confirmed or remained in doubt; b) long-term survivors; and c) patients first admitted when moribund. In contrast, sera were found among the control groups which failed to give positive reactions in dilution 1:10 (18% overall), only few (14%) had levels of ≧1:160, and the geometric mean titer was eightfold lower than that of the confirmed BL cases. The results were similar, whether the controls were: children matched with patients as to age, sex, and tribe; siblings, other family members, and neighbors of patients; or randomly selected. From the age distribution of antibodies to EBV among the controls, it became evident that infections by EBV in East Africa occur in very young age groups at greater frequency than in the United States. Limited numbers of sera from patients with acute malaria, big spleen disease, tonsillitis, leprosy, reticulum cell sarcoma, Hodgkin's disease, or Kaposi's sarcoma yielded results like those seen in the various control groups. The implications of these findings regarding a possible etiologic relation of EBV to BL are discussed.