Because of the new drug combinations being used to treat follicular lymphomas, the small cleaved cell lymphomatous foci in bone marrow biopsies appear to be altered. They become progressively hypocellular and contain a few and sometimes no small cleaved cells within oligocellular paratrabecular fibrous foci. These hypocellular paratrabecular foci (HPF) (a) are a clue that deeper sectioning is necessary to determine whether there are diagnostic foci of residual involvement by small cleaved cell lymphoma, (b) may indicate that other portions of the patient's bone marrow still contain viable foci of small cleaved cell lymphoma, and further, (c) should alert the clinician to the possibility of recurrence of small cleaved cell lymphoma in subsequent bone marrow biopsies. A comparison of patients who developed HPF in one or more of their bone marrow biopsy specimens with those who did not indicates that the changes are related to combinations of chemotherapy other than CHOP-Bleo (cyclophosphamide, adriamycin, vincristine, prednisone, bleomycin). Eighty-one percent of patients who developed HPF had received additional chemotherapeutic regimens, whereas 75% of patients whose bone marrows did not contain HPF had received only CHOP-B. The older age of the HPF-negative patients (median age 64 versus median age 43 for HPF-positive cases) may reflect more aggressive chemotherapy in the younger age group. While HPF appear to reflect some increased chemotherapeutic cytotoxicity affecting the lymphomatous foci in bone marrow, they do not appear to predict for a longer survival or cure.