Persistent generalized lymphadenopathy often develops during HIV‐infection. It is characterized by follicular hyperplasia which progresses over time to follicular involution and finally lymphocyte depletion. To determine whether activated cytotoxic T cells (CD8+) are present in the hyperplastic germinal centres, light and electronmicroscopic immunogold labelling with monoclonal antibodies were used to localize two cytotoxic molecules, perforin and TIA‐1. Perforin and TIA‐1‐positive cells were detected in the follicles and paracortex of lymph nodes from HIV‐infected patients, whereas labelling was seen only in cells of the paracortex in the hyperplastic lymph nodes from HIV‐negative patients. Cytotoxic granules, staining positive for perforin and TIA‐1, were identified by transmission electronmicroscopy, often in proximity to follicular dendritic cells within the hyperplastic germinal centres of only HIV‐positive patients. These cytotoxic cells may play a role in the follicular dendritic cell loss and concomitant follicular involution that occur during the evolution of HIV disease.