We studied follicles in sections of lymph nodes and spleen from cynomolgus monkeys (Macaca fascicularis) after infection with simian immunodeficiency virus (SIVsm), by (immuno)histology and (immunogold) electron microscopy. Also isolated follicular dendritic cells (FDC) were investigated. Histology showed ranged from follicular hyperplasia to follicle fragmentation. FDC showed desmin and vimentin, characteristic of mesenchymal cells. Except for two animals who got experimental chemotherapy in the first postinfection period, the cells expressed SIV gag p28 protein. Electron microscopy showed SIVsm-like particles in the germinal centers. A number of cell types in the germinal center, including FDC, showed tubuloreticular structures, indicative of alpha-interferon synthesis during an antiviral response. In immunogold electron microscopy, SIV p28 label was observed on the surface of FDC, on SIVsm-like particles, and in the cytoplasm of macrophages. A relatively high density of CD8-positive cells (T cytotoxic-suppressor phenotype) was observed around and in germinal centers, especially areas depleted of FDC. Cells immunoreactive for serine esterase granzyme-B, a protein occurring in granules of cytotoxic cells, occurred around germinal centers, but not in germinal centers at areas where FDC and SIV p28 label localized. This argues against a role of cytotoxic T cells in mediating follicle destruction.