Specimens of lymphoid and splenic tissue with reactive changes or involvement by non-Hodgkin's lymphomas or Hodgkin's disease were examined for low-affinity nerve growth factor receptor (NGFR) immunoreactivity of dendritic reticulum cells (DRCs) in frozen tissue and paraffin sections. The DRCs in 13 of 13 specimens with reactive follicular hyperplasia were uniformly immunoreactive with the NGFR-specific antibody NGFR5 and with the DRC-specific antibody DRC-1. We also found that the DRCs associated with 30 of 30 cases of follicular non-Hodgkin's lymphoma were immunoreactive with NGFR5 in a pattern similar to that seen with DRC-1, in contrast to a previous study. Our results were similar in frozen tissue and microwave-treated paraffin sections. Four of four cases of diffuse large cell non-Hodgkin's lymphoma, six of six cases of immunoblastic large cell non-Hodgkin's lymphoma and three of three cases of small noncleaved cell non-Hodgkin's lymphoma did not exhibit significant tumor-associated NGFR5-positive DRCs. Similarly, no NGFR5 staining was observed in eight of eight cases of small lymphocytic lymphoma/chronic lymphocytic leukemia or in six of six cases of marginal zone lymphoma, except in residual germinal centers. However, in 10 of 11 cases of mantle cell lymphoma, the DRCs present in a loose tumor-associated meshwork were reactive with NGFR5; this finding is of potential utility in the differential diagnosis of low-grade lymphoproliferative disorders. In four of four cases of nodular lymphocyte predominance Hodgkin's disease, tumor nodule-associated DRCs were immunoreactive for NGFR in a pattern similar to that seen with DRC-1, but NGFR-positive DRCs were not observed in association with other types of Hodgkin's disease. These results indicate that NGFR expression by DRCs is not lost in follicular non-Hodgkin's lymphomas and mantle cell lymphomas. Nerve growth factor and NGFR may have a role in the function of DRCs and the formation of the DRC matrix in normal and neoplastic lymphoid follicles and in other DRC-associated neoplasms.