An analytical method for the determination of cholesterol sulfate (CS) in plasma using gas-liquid chromatography was developed. We measured plasma CS concentrations in patients with liver cirrhosis and hypercholesterolemia as examples of disorders that involve aberrations in cholesterol metabolism. Patients with liver cirrhosis had plasma CS concentrations that were significantly higher than those of control subjects (444.6 +/- 51.7 vs. 253.0 +/- 24.6 micrograms/dL, mean +/- SE). The levels of other lipids were lower in cirrhotics, although the differences were not significant. There was no correlation between the levels of CS and sulfated bile acids in cirrhotic patients. CS levels in plasma were also higher in subjects with hypercholesterolemia (413.7 +/- 44.5 micrograms/dL); however, the ratio of CS to total cholesterol (TC) clearly differed between cirrhotics and hypercholesterolemic subjects (1.44 +/- 0.11 x 10(-3) vs. 3.31 +/- 0.63 x 10(-3); P < 0.05). Both in subjects with hypercholesterolemia and in healthy controls, the CS/TC ratio was similar and CS accounted for roughly 0.14% of the TC concentration.