In order to compare the polypeptide composition of the CML mature granulocytes with that of the normal whole cell lysates, mature granulocytes from four healthy volunteers and six CML patients were analyzed by two-dimensional gel electrophoresis. In the normal subjects, 60 major spots were commonly and reproducibly identified. In the CML, there were constant alterations in some of these major spots. Four spots were totally absent in all the CML samples, and another four spots were absent in five of the six samples. In addition, one spot was larger in CML than in normal cells, and another spot, which was only faintly visible or not detectable in the normal samples, was massively present in all the CML samples. Our data suggest specific changes in the polypeptide compositions of CML granulocytes. This method could be clinically applied for the analysis of granulocytic disorders.