Epstein-Barr virus (EBV) is associated with many human neoplasms, including Burkitt's lymphoma (BL). Endemic BL in central Africa is more often EBV-associated than BL in the United States, where seroconversion for EBV occurs somewhat later than in Africa. Therefore, the EBV association rate in BL may correlate more with the socioeconomic status of the population studied, which influences the age of EBV seroconversion, than with such factors as malaria, which may relate to the overall higher incidence rate in endemic regions. Forty-one patients with BL in Egypt, which differs both climatically and racially from central African countries (i.e., Kenya, Uganda) where BL is endemic, were analyzed. All biopsies were evaluated for EBV-encoded RNAs (EBER1) by RNA in situ hybridization, analyzed for p53 protein expression using the monoclonal antibody D07, and immunophenotyped using a panel of monoclonal antibodies that included L26 (CD20), Leu 22 (CD43), and A6 (CD45RO). Twelve cases were evaluable for EBV subtype by polymerase chain reaction with EBV-specific primers. The median age at diagnosis was 9 years (range, 2-22 years). The biopsy site was extranodal in 29 patients and nodal in 12 patients. All 41 cases were documented as B-cell neoplasms. A hybridization signal for EBER1 RNA was identified in greater than 95% of the neoplastic cells in 30 of 41 cases (73%), whereas no signal was observed in 11 cases (27%). Epstein-Barr virus subtype 1 was found in 10 patients, subtype 2 in two patients. Immunostaining for p53 was observed in greater than 5% of the neoplastic cells in 9 of 37 cases (24%). No significant correlation was observed between EBV positivity and sex, biopsy site, or p53 immunostaining. The prevalence of EBV in BL from Egypt is slightly lower than in BL in endemic regions, but significantly higher than in sporadic BL. Epstein-Barr virus positivity probably reflects the socioeconomic status of the patient population, and age at seroconversion. The prevalence of EBV subtype 1 suggests that immunodeficiency does not play a role in Egyptian Burkitt's lymphoma, in contrast to endemic Burkitt's lymphoma, in which holoendemic malaria is thought to contribute to immunodeficiency, a higher incidence rate, and the observed prevalence of subtype 2.