The monoclonal antibody 34-5-8S reacts with a conformational epitope on H-2Dd MHC Class I found on the N-terminal domains of alpha1 and alpha2 chains when complexed with beta2-microglobulin. The antibody does not react with H-2Dd alpha chains synthesized in vitro. Weak cross-reactivity with cells from mice of the H-2b, H-2q, and H-2s haplotypes has been observed by flow cytometric analysis. Reactivity with cells from mice of the H-2f, H-2k, H-2p, and H-2r haplotypes has not been observed. 34-5-8S has been reported to block the recognition of H-2Dd by Ly-49A+, Ly-49C+, and Ly-49G2+ natural killer cells.