Synthesis of dipeptides in water, in the solution of water/organic cosolvent and in the binary aqueous-organic system was studied. A set of equlibrium equations was determined and used to predict a product yield. Reagents activities served as variable. Verification of equation's validity was performed in the synthesis of ZAlaPheOMe dipeptide catalysed by thermolysin. The reaction was carried out in water, metanol-water solution and in binary system ethyl acetate - water. It was shown that the synthesis in the binary system was the most effective. It was concluded that the efficiency of ethyl acetate - water system resulted from: 1) improvement of the reagents solubility; 2) product extraction into the organic phase. An insignificant difference in enzyme stability when thermolysin was immersed in water or in the ethyl acetate - water system was observed. Process kinetics in the binary system will be the aim of the next studies.