Lymphocyte egress from the vascular compartment into the lymph node (LN) parenchyma occurs at the postcapillary venules, termed high endothelial venules (HEVs). Lymphocyte adhesion and migration through the HEVs is a receptor-mediated, energy-dependent, process. The aim of this study was to investigate the role of MHC Class II antigen expression on lymphocyte-HEV interaction in normal (CBA) and autoimmune (MRL/l) mice. Using the HEV binding assay, lymphocyte adhesion to LN sections pretreated with monoclonal antibody (MAb; 10-2.16) was decreased compared to diluent (mean of the differences +/- standard deviation; xd +/- SD: 0.749 +/- 0.22, P less than 0.0075)- and myeloma immunoglobulin-pretreated controls (xd = 0.462 +/- 0.13, P less than 0.005). Similar inhibition of binding was found in MRL/l LN sections pretreated with MAb 10-2.16. Binding inhibition was concentration dependent, but total inhibition was never achieved. Several other anti-Ia MAb's were used, but failed to inhibit lymphocyte attachment. Lymphocyte binding to control sections treated with MAb's against MHC Class I antigen, plasminogen activator (PAM-3), anti-thrombin III (AT-IIIm), and MECA-325 antigen was not significantly different from diluent controls. LN cell suspensions pretreated with MAb 10-2.16 bound normally to LN sections. By contrast, MAb to lymphocyte homing receptor (MEL-14) inhibited lymphocyte adhesion. The role of Class II antigens in lymphocyte-HEV interactions is discussed.