Immunophenotypic evaluations of the bone marrow (BM) are reported on 69 aspirates from 58 patients who had non-Hodgkin's lymphoma or chronic lymphocytic leukemia involving the BM. Using flow cytometry and immunofluorescence microscopy on density gradient isolated BM mononuclear cells, the neoplasm could be identified and characterized in 59 aspirates (86%) from 49 patients (84%). Using International Working Formulation guidelines the neoplasms were classified on the basis of prior or subsequent histopathology of lymph node, spleen, skin, or other soft tissue site, or by evaluation of peripheral blood in chronic lymphocytic leukemia. In nine cases the lymphoma could not be completely classified according to International Working Formulation guidelines because only BM was available for evaluation. The neoplasm in the BM was identified and characterized immunophenotypically in all 29 cases of chronic lymphocytic leukemia/well-differentiated lymphocytic lymphoma (WDLL) (100%), in 11 of 12 cases of low-grade lymphoma other than WDLL (92%), in 11 of 15 cases of intermediate-grade lymphoma (73%), and in two of four cases of high-grade lymphoma (50%). Six of the nine cases not classified by International Working Formulation guidelines could be characterized immunophenotypically. In 10 cases immunophenotypic studies revealed negative findings, although the concurrent core biopsy specimens were positive. In two cases immunophenotypic studies with positive findings accompanied a negative core biopsy specimen. A panel of immunohistochemical reagents reactive with fixative/paraffin-resistant antigens was used for a retrospective evaluation of the 69 core biopsy specimens. When compared with the immunophenotypic data obtained from the marrow aspirates these results proved to be only moderately reliable in B-lineage neoplasms and unreliable in T-cell neoplasms. Thus, immunophenotyping of aspirated marrow by flow cytometry was found to be the most reliable method for determining the antigenic profiles of BM-based lymphomas.