Bone marrow (BM) involvement in peripheral T-cell lymphoma was assessed by polymerase chain reaction (PCR)-mediated RNase protection assay. The sensitivity of this assay was approximately 10(-4) to 10(-5). In 16 of 30 patients (53.3%) with peripheral T-cell malignancies, consensus primers for the T-cell receptor (TCR)-gamma gene amplified the rearranged V(N)J region. Using the PCR products of diagnostic lymph nodes of the patients as probes, we analyzed the BM involvement of lymphoma cells in eight patients: four with peripheral T-cell lymphoma, unspecified; two with adult T-cell leukemia/lymphoma; and two with angioimmunoblastic T-cell lymphoma. BM involvement was detected by PCR-mediated RNase protection assay in four patients from BM smear and/or histo-pathological examination of clotted BM. Moreover, in two of four patients in whom BM involvement was not evident from morphological examination, BM involvement was detected by PCR-mediated RNase protection assay. Our results indicate that the PCR-mediated RNase protection assay targeting the TCR-gamma gene is useful in detecting minimal residual disease in about half of all T-cell lymphoma cases. In addition, in some patients with peripheral T-cell lymphoma, morphologically unproven BM involvement was found using the method.