We investigated the expression of adherence molecules lymphocyte function-associated antigens-1 alpha and -beta (LFA-1 alpha, -beta) and p150, 95 in 103 well-characterized non-Hodgkin's lymphomas (NHLs) and lymphoid leukemias (LLs). We found that NHLs and LLs differentially express LFA-1 molecules according to their lineage derivation, degree of clinical aggressiveness, and anatomic site of involvement. Specifically, (a) T-cell neoplasms nearly always express these molecules; (b) diffuse aggressive B-cell NHLs and mature LLs often lack LFA-1 alpha molecules; and (c) B-cell chronic lymphocytic leukemia (CLL) is often LFA-1 alpha-negative while B-cell small lymphocytic lymphomas (SLLs) are nearly always LFA-1 alpha-positive. Furthermore, the low expression of LFA-1 alpha in CLL is related to the low degree of homotypic lymphocyte adhesion after tumor promoter antigen stimulation that does not modulate the expression of LFA-1 alpha in vitro. The differential expression of LFA-1 by B-cell CLL and SLL and their degree of homotypic lymphocyte adhesion may account for the distinct anatomic compartmentalization and characteristic clinical behavior of these two morphologically and immunologically similar lymphoid malignancies.