In the present study, we examined P-glycoprotein (P-gp)-expressing cells in human lymph nodes (LN) from patients with reactive lymph adenitis and various malignant lymphomas (ML). MDR1 mRNA was detected in all reactive LN and in 8 of 10 ML samples examined by reverse transcription polymerase chain reaction (RT-PCR). The signal intensity of the bands was stronger in samples from T-cell ML LN than in those from LN of reactive lymph adenitis and B-cell ML. Immunohistochemistry also showed positive reactivity with cellular components in the LN. The P-gp-positive cells, detected by UIC2, in reactive lymph adenitis and ML samples were large in size in the T-cell-dependent paracortical area in LN. Further, morphological characteristics were similar in UIC2-positive cells between reactive and ML LN. Double staining with UIC2 and a hematopoietic cell lineage-specific monoclonal antibody showed that UIC2-positive cell co-expressed S-100, but not other lymphocyte- and ML cell-specific antigens, indicating that these cells correspond to histiocytes in the T-cell-dependent paracortical area. Our results show that P-gp was expressed in histiocytes but not ML cells in LN, and suggest that this molecule may play an important role in the biological function of histiocytes and/or for maintenance of homeostatic levels in T-cell ML LN.