Frozen tissue sections obtained from human glioblastomas, brain tumor metastases and normal brain were examined for the expression of molecules known to be involved in lymphocyte activation and/or adhesion and migration. The molecules studied included CD3, CD45R, UCHL-1 (CD45RO), lymphocyte function-associated antigen 1 (LFA-1) (CD11a, CD18), intercellular adhesion molecule 1 (ICAM-1) (CD54), 4B4 (CD29), CD44, CD2, and LFA-3 (CD58). CD3+ lymphocytes infiltrating human glioblastomas and brain tumor metastases expressed LFA-1 alpha and beta. Many cells were also UCHL-1+ whereas only a small percentage were CD45R+. CD2+ lymphocytes were also present. Tumor-infiltrating lymphocytes (TIL) were found to be negative for CD29, which was, however, expressed on intratumoral vessels in addition to vessels found in normal brain. Glioblastoma cells and intratumoral vessels expressed ICAM-1 whereas no ICAM-1 was found on TIL or on normal brain. Glioblastoma cells also expressed high levels of both CD44 and LFA-3 whereas TIL were negative for these antigens. CD44 was also expressed on certain regions of normal brain. Antibodies to LFA-1 alpha and -beta and ICAM-1 could significantly block the binding of lymphokine-activated killer (LAK) cells or TIL to human glioblastoma cells suggesting that these molecules play a role in the binding and subsequent migration of lymphocytes into brain tumor tissue.