A method of quantitative determination of peptides and proteins by ESI-MS at picomolar levels was developed. The essence of the method consists in determination of the concentration of individual amino acids from the analyzed proteins. Proteins were first subjected to hydrolysis (acid or enzymatic) and then we measured  relative ion intensities of amino acids and their isotope labeled analogs. As internal standards, the Î18-containing analogs for 5 amino acids, and also deuterated lysin and arginine modified by nitrogen 2N15 were used. The method is applicable to proteins with known amino acid sequences. This method was tested by the determination of concentration of bovine serum albumin (BSA), chemotrypsinogen and proinsulin.