Primary biliary cirrhosis (PBC) is a chronic cholestatic disease in which there is a crucial need for quantitative liver-function tests. We have developed a mixed sulfobromophthalein (BSP)-indocyanine green (ICG) test and have applied it to 15 healthy subjects and 50 patients with PBC to determine its relevance to the histological severity of the disease. The two dyes were administered intravenously and sequentially as boluses. Plasma concentrations were measured over 60 min. Pharmacokinetic analysis of the plasma elimination curve permitted the calculation of clearance, constants k1 and k2, and the retention percentage at 45 min. In PBC patients, ICG kinetics were within the normal range except for those with stage IV disease (cirrhosis). BSP clearance and the k2 constant were reduced in all the patients, whereas the k1 constant was reduced only in stage III and IV disease. The BSP retention percentage at 45 min was highly correlated with histological stage (r = 0.89, P less than 0.001). The BSP-ICG mixed test may thus prove useful in the diagnosis and follow-up of patients with PBC.