The cell lineage of suspensions prepared from 85 non-Hodgkin's lymphomas was investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin, assessed with specific heteroantisera, proved to be the most useful characteristic and defined the clonal character and B-cell lineage of 63 specimens: almost all nodular lymphocytic (21 of 22) and diffuse lymphocytic (11 of 13) lymphomas, most diffuse histiocytic (29 of 33) and diffuse mixed (2 of 2) lymphomas, and a few nodular mixed (2 of 12) and nodular histiocytic (0 of 3) lymphomas. Monoclonal antibodies provided useful ancillary surface marker criteria. Thus, positivity with OKT1 (which detects both thymic and peripheral T cells) in the absence of reactivity with monoclonal antisera, which detect only peripheral T cells (OKT3, OKT4, OKT8, and OKT11), was seen only in diffuse lymphocytic lymphoma of B lineage. Ia-like antigen could be demonstrated in all B-cell lymphocytic lymphomas and most B-cell diffuse histiocytic lymphomas. Approximately one-half of diffuse histiocytic lymphomas also reacted with OKT9, which detects the transferrin receptor, while few lymph nodes involved by other conditions displayed this reactivity. Most diffuse histiocytic lymphomas and many non-Hodgkin's lymphomas of other subtypes reacted with OKT10, an antiserum that detects an antigen on replicating lymphoid cells. The lineage of approximately one-fourth of the lymphoma suspensions was not resolved conclusively: In most of these, T lymphocytes predominated with a normal proportion of inducer-helper (OKT4) and cytotoxic-suppressor (OKT8) cells. The inability to establish the clonal character of T-cell proliferation in cell suspensions remains an obstacle to completely defining the lineage of non-Hodgkin's lymphomas.