Abstract Bilirubin production rate (BRP) and total red cell volume (TRCV) were determined simultaneously on 70 occasions in 56 individuals. The population studied included 16 normal volunteers and 40 patients with a spectrum of disease states. Mean red cell life span (RBCLS) was calculated from BRP and TRCV using the assumption that 85 per cent of bilirubin production resulted from catabolism of the hemoglobin of circulating red blood cells. The validity of this assumption in most disease states was indicated by (1) the high degree of correlation between RBCLS and independent measurements of red cell survival using DFP- 3 H (di-isopropylfluorophosphate) (r = 0.98), 59 Fe ferrokinetics (r = 0.85), and 51 Cr red cell halflife (r = 0.85), and (2) the results of 9 studies in which the peak protoporphyrin/urobilin (PU) specific activity ratio and/or the early labeled peak were determined directly following the administration of glycine 2- 14 C. The assumption is not valid in the few conditions characterized by increased ineffective erythropoiesis. In normal adult volunteers, RBCLS averaged 104 ± 14 days (mean ± S.D.), and was shorter in women than men. These studies suggest that measurements of BRP and TRCV can provide a rapid and accurate measure of red cell survival in most patients.