The phenotype of follicular dendritic reticulum cells (DRC) was analyzed with monoclonal antibodies (DRC-1, OKB7, BA-2, Leu-M3, and antidesmoplakin 1 and 2) in 28 frozen biopsy specimens of both morphologically and phenotypically analyzed B-cell lymphomas and 21 normal or reactive controls. The former included 15 follicular center cell lymphomas (FCCL), four intermediately differentiated lymphocytic lymphomas (ILL), four mantle zone lymphomas (MZL), and five well-differentiated lymphocytic lymphomas (WDLL). In controls, DRC-1+ and OKB7+ DRC were localized in both follicular centers (FC) and mantle zones (MZ), but BA-2+ and Leu-M3+ DRC were confined to FC only. FCCL were usually accompanied by DRC-1+, OKB7+, and BA-2+ DRC, and either lost or maintained positively with Leu-M3 from case to case. By contrast, MZL consistently lacked BA-2+ and Leu-M3+ DRC, and was associated with DRC-1+ and OKB7+ DRC only. Desmoplakin-positive DRC occurred in variable proportions in both FCCL and MZL. As opposed to FCCL and MZL, all WDLL and all but one of the ILL (associated only with DRC-1+, OKB7+, and desmoplakin+ DRC) did not show any DRC as identifiable with the antibody panel used. Remarkably, the difference in the distribution of BA-2+ and Leu-M3+ DRC in the normal FC and MZ appears to be maintained in their neoplastic counterparts (FCCL and MZL) also. Such a difference represents an example of the possible interactions between lymphoma cells of different phenotype and their microenvironment, as portrayed by phenotypically heterogeneous DRC.