Peptide synthesis catalysed by papain was studied using thio‐α‐amino acids (S‐acids) as a carboxyl component. It was found, for example, that with Z‐AlaSH (pK 2.70) the maximal yield of the peptide Z‐AlaValNH2 was obtained at pH 8–8.5. A two‐fold excess of Z‐AlaSH furnished peptides with yields close to 100%. Thio‐amino acids with bulky side groups, for example, Z‐IleSH, Z‐Asp(OBut)SH, gave peptides with a low yield. Papain interacts with Z‐AlaSH better than do bromelain or ficin.