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Using a rapid, highly sensitive immunoprecipitin nephelometric technique, a retrospective study was undertaken to evaluate the clinical usefulness of determining serum haptoglobin in the diagnosis of hemolysis. Haptoglobin assays were performed shortly after admission in 100 patients with a variety of hematologic and nonhematologic conditions and the results correlated with the clinical diagnosis. An ad hoc boolean computer program allowed for the separation of hemolytic from nonhemolytic disorders with a haptoglobin limit of 25 mg/dL or less. The sensitivity and specificity of the test are high (83% and 96%, respectively), providing 87% probability of predicting hemolytic disease when the serum haptoglobin level falls below this limit. These data support the routine use of serum haptoglobin determinations in the diagnosis of hemolytic disease.