The potential usefulness of an optimalized high-resolution two-dimensional gel electrophoresis (2-DGE) protocol was studied by comparative analysis of plasma/serum obtained from apparently healthy individuals and from patients with a few selected known diseases. Despite their apparent complexity, patient electrophoretograms revealed readily detectable modifications of the 'reference' protein profile for those selected diseases (listed below). Abnormal profiles were characterized by presence or absence of particular spots, by reduction or enlargement of spot size, or by alterations of spot microheterogeneity. Combinations of several modifications enabled different 'disease-associated spot pattern' to be distinguished on the protein maps of patients with: monoclonal gammopathies, hypogammaglobulinemia, hepatic failure, chronic renal failure and hemolytic anemia. This study demonstrates that identification of plasma/serum protein alterations by 2-DGE allows a few selected diseases to be diagnosed solely on the basis of protein map modifications.