Sixteen cases of intermediate lymphocytic lymphoma (ILL), including eight cases with mantle zone architecture, were studied using cryostat sections, a biotin-avidin immunoperoxidase technique, and a large panel of monoclonal antibodies. The neoplastic cells invariably expressed IgM, most B lineage antigens (B1, TO15, Leu-12, 6A4, 41H, BA-1, and LN-2), and Ia. IgD was expressed in 12 cases. Leu-1 and Leu-8 were weakly expressed by the tumor cells in 12 and 11 cases, respectively. The neoplastic cells did not express common acute lymphoblastic leukemia antigen (CALLA) or the T10 antigen in any case. Because ILL is difficult to differentiate from small lymphocytic lymphoma (SLL) and diffuse small cleaved cell lymphoma (DSCCL) on the basis of light microscopic criteria, the immunologic findings of ILL were compared to 31 cases of B cell SLL and 11 cases of B cell DSCCL previously studied in the laboratory to determine if immunologic findings might aid in the distinction. No absolute, and five statistically significant, differences were found; IgD in combination with IgM was seen more commonly in cases of ILL and DSCCL than in SLL (P less than .01), IgG was found more often in SLL than in ILL and DSCCL (P less than .05), Leu-8 was more commonly expressed in ILL and SLL than in DSCCL (P less than .05), T9 expression was less frequent in ILL as compared with SLL (P less than .05) and more proliferating cells were seen in ILL and DSCCL than in SLL (P less than .01). The investigators conclude that these three classes of lymphoma are remarkable much more for their immunologic similarities than for their differences and that immunologic studies are of limited usefulness in differentiating the three neoplasms. Their results also support the concept that these lymphomas are closely related to each other. In particular, DSCCL immunologically appears to be more closely related to SLL and ILL than to follicular small cleaved cell lymphoma.