Abstract: Gene segments of human T cell lymphotropic virus type III (HTLV-III) were expressed in E. coli as peptides that are reactive with sera from patients with acquired immune deficiency syndrome (AIDS). Among recombinant peptides one designated HTLV-III polypeptide 121, contained 85 amino acid residues encoded by a gene segment in the env-lor region of the HTLV-III genome. The polypeptide is strongly reactive with AIDS patient sera. The peptide produced and purified as a fusion protein on a large scale. Solid phase immunoassays employing this recombinant peptide as an immunoabsorbent can reliably and reproducibly detect antibodies in sera of patients with HTLV-III infection. In two representative serum panels, the assay detected the presence of antibodies in 120 of 121 sera from patients with AIDS or AIDS-related complex (ARC), and only in 1 of 92 normal controls. Based upon HTLV-III polypeptide 121 as immunoreactive agent, sensitive and specific immunoassays for HTLV-III infection have been developed.