To reevaluate the diagnostic significance of a markedly elevated erythrocyte sedimentation rate (ESR), the clinical diagnosis associated with an ESR of 100 mm/hr or greater was retrospectively analyzed in 200 patients at the Massachusetts General Hospital. In contrast to previously reported experiences in the the American literature suggesting a high frequency (58 percent) of malignant disease in such patients, the present study found infections to be the most frequently associated diseases (35 percent), while malignant disease accounted for only 15 percent of the patients. Review of the foreign literature similarly suggested infection rather than malignancy as a major association with markedly elevated ESRs. It is concluded that an ESR greater than or equal to 100 mm/hr has little diagnostic specificity and should not of itself dictate evaluation for occult malignancy in most patients.