L ymphocyte homing receptors (HRs) defined by Hermes antibodies (anti-CD44) and lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18) are involved in lymphocyte binding to endothelial cells of high endothelial venules (HEVs) at sites where lymphocytes exit the blood. Their expression was correlated to the clinical behavior of 245 non-Hodgkin's lymphomas followed up for the median of 87 mo after the diagnosis. Lymphomas that showed no or weak staining intensity for HRs were more often of stage I (P = 0.005), disseminated less frequently hematogenously (P = 0.003), and had more favorable prognosis than lymphomas with intensive staining for HRs (P less than 0.0001) despite that they were more often histologically of high grade malignancy (P = 0.002). Expression of LFA-1 beta chain (CD18) did not correlate significantly with stage or survival, but had prognostic value in a subgroup of HR expression negative lymphomas (P = 0.03). HR staining intensity was an independent prognostic factor in a multivariate analysis. These findings indicate that Hermes/CD44 molecule is associated to the determination of the metastatic potential and prognosis of non-Hodgkin's lymphomas. They also reveal a new entity among non-Hodgkin's lymphomas, because lymphomas that express low levels of HR have favorable prognosis despite their often highly malignant histological appearance.