In order to evaluate the clinical significance of very high erythrocyte sedimentation rates (ESRs) we studied 100 consecutive men in a VA Medical Center whose Westergren ESR was more than 100mm/hr. All were followed for up to six months and the ESR-requesting physicians were interviewed. A total of 162 diagnoses known to be associated with an elevated ESR were present in the 90 patients available for follow up. As in most previous series on very high ESRs, infections (seen in 43 patients) were the most common diagnoses. Other diagnoses included: malignancy (16), rheumatologic disease (30), other inflammatory diseases (seven), renal disease (25), and miscellaneous problems (38). Evaluation of 16 patients led to a diagnosis that had not initially been apparent--the ESR-requesting physician did not consider that a high ESR was instrumental in guiding him towards any of these delayed diagnoses. Most of the markedly elevated ESRs in this patient population, requested in the context of already evident serious multisystem disease, contributed little diagnostic information.