The diagnostic value of the enzymatic fluorometric method for total serum bile acids (TSBA) and for radioimmunoassay measurement for conjugated cholic acid (CCA) or chenodeoxycholic acid was compared with that of routine liver function tests in 223 patients with liver disease, 88 healthy subjects, and 118 patients affected by other diseases. The value of the tests for screening in the general population was assessed by simulation, using estimates of disease prevalence. TSBA was significantly more sensitive (78%) but less specific (94%) than CCA (sensitivity of 69%, specificity of 98%). Aspartate aminotransferase was nearly as sensitive (74%) as TSBA, but significantly less specific (93%) than CCA. CCA provided the highest positive predictivity (98%), even in a screening simulation (32%). With the use of sequential aspartate aminotransferase measurement followed by CCA, this value rose to 100%. This test procedure appears to be the best screening method for liver diseases available at present.