Two-dimensional electrophoresis is increasingly being used as an important tool for biological research although it continues to have few direct clinical applications. In the absence of simple systems to identify and quantify individual proteins or groups of proteins it is unlikely that clinical applications will increase. Measurement of some individual proteins, for example a single acute phase reactant, often yields as much clinically useful information as could be currently expected from quantitation of several proteins with the same physiological role. Cost-containment pressures within the clinical laboratory will prevent the technique from becoming widely used in the clinical laboratory until it can clearly demonstrate that it can produce clinically important and necessary information that can not be obtained by other means. We continue to believe that the technique's greatest potential lies in identifying a protein or proteins whose concentration can be correlated with a disease and whose concentration varies with the progress of the disease. Antibodies to such proteins can then be produced and used to quantify the disease-associated proteins by a simple procedure, such as nephelometry. In spite of our belief of the likely clinical application of the technique there appears to be no systematic use of two-dimensional electrophoresis for this purpose. With clinical specimens a few investigators still run gels of serum or urine from patients with apparently unusual disorders and compare them visually with gels from healthy individuals. Nevertheless, the technique continues to have considerable unmet promise for clinical applications.