1. The concentrations of plasma total and unconjugated bilirubin and of serum non-esterified fatty acids (NEFA) have been measured in two healthy subjects during fasts of up to 21 h.
2. Fasting was either continuous or interrupted by various procedures that altered the concentrations of NEFA and total bilirubin.
3. When NEFA concentrations were increased by the administration of noradrenaline, heparin or caffeine, bilirubin concentrations also rose.
4. When NEFA concentrations were lowered by insulin, bilirubin concentrations fell.
5. Meals of 3·138 kJ and more, taken during the fasting period, lowered total bilirubin and NEFA concentrations in both subjects, whereas the effects of smaller meals were less consistent.
6. These studies demonstrate a statistically significant correlation between total bilirubin and NEFA during uninterrupted fasting and an association between these variables under other experimental conditions. They suggest that the control of bilirubin concentrations in the blood is linked to lipid metabolism.