OBJECTIVE To investigate whether follicular dendritic cells (FDC) are target cells for HIV-1 infection. METHODS Based on the principle that if FDC are true target cells, HIV-1 particles will bind to the surface of FDC and then invade their cytoplasm and nuclei. METHODS Freshly isolated tonsilar FDC were exposed to two strains (HE and JR-FL) of HIV-1 and cultured. They were then examined for HIV-1 replication, using p24 antigen-capture enzyme-linked immunosorbent assay, immunolabelling, and polymerase chain reaction (PCR) amplification. We used FDC clusters as the FDC source, since the culture system for FDC clusters has various advantages over other methods for the successful long-term culture of FDC. RESULTS After 2 h incubation, particles of both HIV-1 strains bound to the surfaces of FDC, as well as to CD4+ T cells, although FDC do not have CD4 receptors. The FDC gradually released the particles into the culture supernatant. More HIV-1 particles were bound to fresh FDC than to dedifferentiated FDC or to control fibroblasts. However, HIV-1 particles bound to the FDC did not seem to enter the cells. We found no evidence of HIV-1 proviral DNA synthesis in FDC. CONCLUSIONS Our results suggest that FDC are not readily infected with HIV-1 in situ, although we found that FDC in vitro were not infected by HIV-1.