Immunospecific magnetic microspheres, consisting of ferromagnetic iron dextran conjugated to Protein A, were used to specifically label red blood cells (RBC) for cell separation studies using high gradient magnetic chromatography ( HGMC ). When 10(7)-10(8) RBC labeled with Protein A-iron dextran microspheres were applied to a column containing 30 mg stainless steel wire placed in a 7.5 kilogauss magnetic field, 96 +/- 2% of the cells were retained in the column. These cells could be eluted by removing the magnetic field and mechanically agitating the column. The retention of labeled cells by HGMC was shown to be dependent on the applied magnetic field and the amount of wire packed into the column. HGMC in conjunction with cell labeling with immunospecific iron dextran microspheres have useful applications for the separation of specific cell types.