In Uganda, a large number of biopsied enlarged lymph nodes is diagnosed as reactive lymphoid hyperplasia (RLH) not indicative of a specific etiologic agent. The aim of this study was to examine the spectrum of RLH in lymph node biopsies in Ugandan patients and their possible association with HIV and EBV infection. Ninety biopsies were retrieved and included in the study. The predominant RLH type was follicular, found in 45 (50.0%) of the cases. Positive staining for LMP-1 was found in six cases (6.7%), EBNA-1 in 36 cases (40.0%) and HIV1-p24 in 15 cases (16.7%), respectively. A combination of EBV and HIV positivity was found in 46 (52.2%) of the cases. EBV infection was associated with hyperplastic germinal centers (p<0.01). HIV1-p24 positive staining was associated with follicle fragmentation (p<0.01) but not hyperplastic GC (p=0.08). In conclusion, RLH in Ugandan patients is frequently associated with EBV and HIV infection. The histologic features of the lymph nodes are not specific for any individual infection, but a high number of EBV-positive cases are associated with hyperplastic GC, and follicular fragmentation is characteristic of HIV infection.