Human immunodeficiency virus (HIV) strains can be separated into two types: HIV and HIV-related West African viruses. Site-directed serology using synthetic peptides offers possibilities for the determination of type-specific antibodies. A 22-amino-acid peptide with the sequence Ala-Ile-Glu-Lys-Tyr-Leu-Glu-Asp-Gln-Ala-Gln-Leu-Asn-Ala-Trp-Cys-Ala-Phe-Arg-Gln - Val-Cys representing a conserved region of the transmembranous protein of simian T-cell lymphotropic virus-type III (STLV-III; related to West African HIV) was used as antigen in an enzyme-linked immunosorbent assay (ELISA). In parallel, tests were performed with a pair of previously described peptides, including the homologous region of the glycoprotein (gp) 41 of the HIV strain HTLV-IIIB. In tests with three groups of 20 sera it was shown that the different peptide ELISAs allowed a categorical distinction of antibodies to the two types of HIV. Tests using peptide antigens may provide excellent opportunities for large-scale testing for type-specific antibodies against HIV. The tests are simple, sensitive and specific and are readily standardized.