Twelve human monoclonal immunoglobulins were separated and purified through the use of cryoprecipitation, salt fractionation, electrophoretic separation and gel filtration. Monoclonal cryoglobulin was the easiest form of homogeneous immunoglobulin to isolate. IgG and IgM were generally purified by salt precipitation and ion exchange chromatography followed by G-200 gel filtration. IgA purification required tedious recycling procedures. The purification of IgD posed the most difficulty as it may degrade spontaneously. Monoclonal immunoglobulins differed markedly in their behaviour towards enzymatic digestion, due to a rather wide specificity of enzymes on the Fc fragment. IgG was usually enzyme-sensitive, while some IgA proteins were virtually enzyme-resistant. The Fab fragment usually retained its antigenicity, but Fc or Fc' often split into small peptides. The reductive cleavage of monoclonal proteins usually gave consistent results, and H and L chains were separated in all experiments. However, 5 to 15% of IgA was at times eluated in unreduced form, and the alpha chain was often filtered as a dimer form. L chains were always eluated as a monomer form.