The migration of radiolabeled intravenously injected B lymphocytes through thymus-dependent areas was studied in lymphoid organs of mice with experimentally defined T cell domains (B cell-deprived mice or "T" mice). In the spleen, B cells were found to enter the peri-arteriolar lymphoid sheath (PALS) by two routes: (i) via the marginal zone, and (ii) via reticulum sheaths surrounding terminal arterioles. B cells migrated through the peripheral and central PALS and initiated the formation of primary follicles in the peripheral PALS 6 h after injection. Distinct primary follicles were noted at 18 h after injection of the labelled B cells. After 24 h small numbers of labelled cells were also noted in the efferent lymphatic vessels of the spleen. The reconstitution of B cell compartments in the mesenteric lymph node was delayed compared to the spleen. B cells entered the nodal stroma across the wall of high endothelial venules in the paracortex and by 6 h were found scattered throughout the paracortex. Isolated clusters of a few labeled cells were noted in the outer cortex at 18 h after cell transfer. Defined primary nodules were seen only 24 h after reconstitution. A minority of labeled cells was found at 24 h in the cortico-medullary junctions and in medullary cords. The present study shows that B lymphocytes traverse T cell domains on their way to their own specific B cell compartments. The immunological significance of this particular migration route is discussed in view of data on the cellular cooperation of B cells, T cells and macrophages during the humoral immune response.