Patients with documented serious infection and total bilirubin values of greater than 2 mg/dl were surveyed for serial changes in bilirubin and other laboratory and clinical features. Of 19 patients studied, 12 (Group A) had persisting or increasing hyperbilirubinemia, and 7 (Group B) had decline in bilirubin after infection onset. None demonstrated marked changes in other liver tests. Only one patient had infection directly involving the hepatobiliary system. There were no significant differences between the two groups with respect to underlying illnesses, active hepatobiliary diseases, pathogens, bacteremia, or administration of cholestatic drugs. All Group A patients died because of uncontrolled infections, whereas all Group B patients survived with resolution of infection (p less than .001). Ten of 15 patients with available preinfection liver tests demonstrated serial bilirubin increases without marked changes in other liver tests prior to clinical recognition of infection. These findings demonstrate that hyperbilirubinemia disproportionate to increases in other tests may manifest before recognition of infection and that persistent or progressive hyperbilirubinemia is indicative of ongoing active infection.