Cells from spleens and lymph nodes infiltrated with neoplastic well-differentiated lymphocytes (WDLT) were investigated for the presence of receptors for unsensitized sheep red blood cells, complement (IgM EAC), and antigen-antibody complexes, as well as for the presence of surface immunoglobulins. In addition, the cells were examined by scanning electron microscopy (SEM). The surface markers and ultrastructure of WDLT cells were compared with those of cells obtained from peripheral blood of patients with chronic lymphocytic leukemia (CLL). Like the CLL populations, most WDLT samples showed a low percentage of unsensitized sheep red blood cell-binding cells and a concomitantly high percentage of IgM EAC-binding cells. Furthermore, a substantial number of WDLT cells in several instances showed a lower binding affinity for IgM EAC than normal lymphocytes, as demonstrated by the poor attachment of the IgM EAC reagent to the WDLT cells in suspension and to frozen tissue sections. Weak IgM EAC binding capacity was demonstrated in the CLL cells as well. WDLT and CLL cells bound the IgG EA complex only when certain sensitive techniques were applied (pelleting). A variable percentage of cells with surface immunoglobulins was found among WDLT and DLL populations. However, accurate counting of surface immunoglobulin-bearing neoplastic cells was very difficult in most cases due to the extremely faint surface fluorescence as compared to normal. SEM did not reveal specific changes in WDLT or CLL cells that would permit their identification as neoplastic lymphocytes. No major differences were found between WDLT and CLL cells and no correlation could be established between SEM appearances and surface markers. As previously observed with other cell populations, the conditions under which the cells were manipulated before fixation (in particular the environmental temperature) seemed to play a major role in the final SEM appearance of both WDLT and CLL cells. The results of our studies indicate that WDLT cells represent a population of B-cells whose surface properties are very similar to those of circulating CLL cells. The poor capacity of WDLT cells and CLL cells to bind IGM EAC or to stain with fluorescein-conjugated antihuman immunoglobulin suggests low density or poor affinity of the surface receptors. In this regard, these neoplastic cells are different from those of follicular lymphomas, also of B-cell origin.