In order to identify and characterize the sheep major histocompatibility complex (MHC) class II molecules, a panel of 19 monoclonal antibodies (mAb) has been raised following immunization of mice with a variety of class II antigen preparations. Antibodies were selected by ELISA using immunopurified sheep class II as antigen and further screened for the ability to react on immunoblots. Nine mAb reacted with the beta-chain and four reacted with the alpha-chain. The chain specificity of the remainder could not be determined as they did not blot. The anti-alpha and anti-beta mAb all reacted with deglycosylated class II. With the exception of one anti-alpha and one anti-beta antibody, the antibodies reacted with both efferent lymph cells and peripheral blood mononuclear cells (PBMC). Three of the anti-sheep class II mAb reacted with human PBMC.