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To identify factors affecting bilirubin excretion, the effects of bile flow and bile salt excretion on bilirubin output into bile have been examined in normobilirubinemic, cholecystectomized patients with balloon-occludable, reinfusion T-tubes, 8 patients with cholesterol (CS) and 2 with pigment (PS) gallstones. Another patient with pigment gallstones, sickle cell disease (SS), and stable jaundice was studied to examine the mechanism by which an increased bilirubin load was excreted. Total bilirubin was almost entirely conjugated and excretion was related linearly to bile salt excretion in PS and CS subjects; one-third of bilirubin excretion was bile salt independent and two-thirds was bile salt associated. In the SS patient 90% of the bilirubin excretion was independent of bile salt output. In PS and CS patients, bilirubin output was linearly related to bile flow, but the SS patient showed significant bilirubin excretion at low flow rates. CS and PS patients had similar patterns of bilirubin excretion, but the increased bilirubin load in the SS patient was excreted entirely independently of bile salts. In the SS patient, unconjugated bilirubin output was hyperbolically related to bile salt output and represented a maximum of 3% of the total bilirubin output. The bile salt-independent excretion of conjugated bilirubin suggests that micelles were not required for transport into bile; whereas the hyperbolic relationship for unconjugated bilirubin and bile salt output, similar to that of the micellar lipids, cholesterol, and phospholipids, suggests interaction with micelles.