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Non-Hodgkin's lymphomas occurring in AIDS patients (AIDS-NHL) are known to be highly associated with Epstein-Barr virus (EBV). However, there have been no previous detailed studies of the distribution of EBV-infected non-neoplastic lymphoblasts, which may act as precursors of AIDS-NHL. In the present study, an attempt was made to detect such EBV-infected cells in patients' lymphoid organs. Fifteen non-neoplastic lymph nodes obtained from HIV-positive individuals were processed for in situ demonstration of EBV-encoded small RNA (EBER-1) and EBV-encoded latent membrane protein 1 (LMP-1). An increased number of EBER-1-expressing cells were observed (9/15). EBER-1-positive cells were present much more frequently in advanced cases, as evaluated using the histopathologic criteria of Grundmann (1/6 cases showing irregular follicular hyperplasia; 3/4 showing the beginning follicular destruction; 2/2 showing progressive follicular destruction; 3/3 showing follicular involution). LMP-1 was detected in 3/9 EBER-1-positive cases, and all three of these cases were at the most advanced stage. Furthermore, cells expressing LMP-1 were larger (62.83±6 μm2) than EBER-1+ LMP-1− cells (29.05±7 μm2). These results indicate that cells with latent expression of the EBV gene increase in number in lymphoid organs of HIV-infected individuals at an advanced stage and that some of the cells are in a transformed state. It is possible to speculate that these cells are precursors of AIDS-NHL.