Charts of 1006 consecutive outpatients were reviewed to ascertain the cause of extreme elevation of the erythrocyte sedimentation rate (ESR) (greater than or equal to 100 mm/h) and the sensitivity of marked ESR elevation in patients with disorders commonly reported to cause ESR elevation. Prevalence of ESRs of 100 mm/h or more was 4.2%. Infection was the most common cause (33%), with malignant neoplasms and renal disease each responsible for 17% and inflammatory disorders for 14%. Only 1% of all other patients had ESRs of 100 mm/h or more. An ESR of 100 mm/h or more had low sensitivity: 36% among patients with infection, 25% among those with malignant neoplasms, and 21% among patients with noninfectious inflammatory disorders. Specificity was high, both for individual disease categories (96% for malignant neoplasms and 97% for infection) and as a "sickness" index (greater than 99%). The positive predictive value for an identifiable cause of marked ESR elevation was 90%.