We attempted to select monoclonal antibodies (mAb) which reacted with T-cell surface molecules and were able to interfere with the human immunodeficiency virus type 1 (HIV1) replicative cycle in the MT4 T-leukaemic cell line. In comparison with OKT4A, an anti-CD4 mAb, only one mAb, HC11.151.1, was found to significantly delay HIV-induced cytopathic effect on MT4 cells among the 15 mAb tested which reacted with MT4 cell surface antigens. Biochemical and immunological characterization of HC11.151.1 demonstrated its specificity for beta 2-microglobulin (beta 2m), the light chain of human leukocyte antigen (HLA) class I molecules. Other beta 2m-specific mAb were tested in order to assess whether this effect represented an intrinsic capacity of HC11.151.1 or whether it was a common feature shared by all anti-beta 2m mAb. Three (B1.1G6, B2.62.2 and BBM1) of the four anti-beta 2m mAb demonstrated the same protective effect, whereas C21.48A, which was devoid of a functional effect, was directed towards a beta 2m epitope involved in binding to the HLA class I heavy chain molecule. The physiological relevance of this observation is discussed.