Extranodal non-Hodgkin's lymphoma in the head and neck, especially T-cell lymphoma of the lethal midline granuloma (LMG) type, has unique clinical and histologic features differentiating it from other lymphomas. The authors measured soluble intercellular adhesion molecule-1 (ICAM-1) in sera from 12 patients with T-cell lymphoma of the LMG type and from 52 patients with other head and neck non-Hodgkin's lymphomas, by double-determinant immunoassay. The expression of ICAM-1 in lymphoma tissue was examined in 26 patients by the avidin-biotin immunoperoxidase method. The serum ICAM-1 levels were significantly higher in T-cell lymphoma of the LMG type than in other head and neck lymphomas or in healthy adult controls. Elevated levels of serum ICAM-1 were associated with increased levels of serum lactate dehydrogenase, poor prognosis, and impaired T-cell-dependent immune functions, both in T-cell lymphoma of the LMG type and in other head and neck lymphomas. When we monitored serum ICAM-1 levels in individual patients, the level decreased in the complete remission interval compared to before treatment and went up again when the lymphoma relapsed. Although the staining intensities of ICAM-1 in lymphoma cells were not related to serum ICAM-1 levels, a markedly intense expression of ICAM-1 was found on the angiocentric or angiodestructive lymphoreticular infiltrate region in the tissues from T-cell lymphoma of the LMG type. A higher serum ICAM-1 level and its tissue expression in T-cell lymphoma of the LMG type may be one of the clues to understanding this particular lymphoma. The serum ICAM-1 level could be an efficient parameter for monitoring the clinical course of head and neck non-Hodgkin's lymphomas.