Affinity of lymphoid cells for the microenvironment of germinal centers (GC), as detectable in transfer experiments by rapid homing in spleen GC from the blood, is a capacity expressed by only a subset of lymphoid cells, in particular by those constituting a GC. However, when introduced into the blood stream, these cells do not home into GC of lymph nodes and gut-associated lymphoid tissues. To investigate further this homing inability for high endothelial venule (HEV)-containing lymphoid tissues, GC cells isolated from donor rabbit appendix were labeled in vitro with 3H-leucine and injected into an afferent lymph vessel of recipient popliteal lymph nodes. Draining lymph nodes were removed 15 min to 24 h after cell administration and prepared for radioautography. For reference, the migration of cells isolated from Peyer's patches and thoracic duct lymph was also studied. By use of appendix GC cells, large numbers of labeled cells were found to migrate into GCs of the outer cortex centripetally, i.e., from the subcapsular sinus through the lymphocyte corona into the GC proper. The same was observed for cells from Peyer's patches, although in smaller numbers. Thoracic duct lymphocytes were only localized in the lymphocyte corona and the deep cortex. Thus, appendix GC cells and a subpopulation of cells from Peyer's patches can reach lymph node GC, but only when administered intralymphatically. We conclude that cells expressing affinity for the GC microenvironment do so for both spleen and lymph node GC, but do not have the capacity to interact with the wall of HEV; its implication for the understanding of the dynamics of a GC reaction is discussed.