In 141 patients with African Burkitt's lymphoma, the relationship between Epstein-Barr virus (EBV)-related antibody titers and the clinical course of this disease was presented. Antiviral capsid antigen tests gave positive results in all patients, siblings, and control neighbors; but the geometric mean antibody titers to viral capsid antigen were significantly higher in patients than in siblings or neighbors (P less than 0.001). No control neighbors or siblings had antibodies to restricted (EA-R) or diffuse (EA-D) early antigen. Mean geometric anti-EA-R titers at admssion and at last visit were significantly lower in patients with stage (I and II) than in those with stage (III and IV) disease; this most likely reflected the degree of tumor burden. Patients who relapsed after 1 year of sustained remission had significantly higher anti-EA-R titers than did those who did not. The increase in the probability of relapse was sixfold for those patients with an anti-EA-R titer of greater than 160 after 1 year of sustained remission. Survivors and nonsurvivors differed significantly in the final EA-R and Epstein-Barr virus nuclear antigen (EBNA) titers (P less than 0.05 and P less than 0.001, respectively). Anti-EA-D titers were particularly likely to be positive in patients with multiple relapses. When skin reactivity to an antigen from RAJI cells was compared to EBV-related serologic reactions in the same patient, a significant inverse correlation (P less than 0.001) between skin reactivity and EBNA titers appeared. Pretreatment sera from patients with high EBNA titers did not block skin reactivity to the RAJI antigen.