The distribution of [3H]taurocholate between albumin and the lipoproteins of serum of patients with various diseases in which lipoprotein metabolism and/or bile salt concentrations were altered and of healthy control subjects was investigated by means of the density gradient centrifugation method. 1. In control sera, bile salts distribute mainly between albumin and high-density lipoprotein. An amount of 19.7 +/- 3.6% (mean +/- S.D., n = 6) of the total serum bile salts was found in the high-density lipoprotein fraction of the density gradient. 2. In sera of nonicteric patients, the distribution pattern of [3H]taurocholate in the fractions of the density gradient showed no essential differences to normal serum. The relative amounts of taurocholate in the albumin-containing fractions and the high-density lipoprotein fractions were dependent on the concentrations of albumin and high-density lipoprotein. 3. In sera of deeply jaundiced patients, the distribution pattern of [3H]taurocholate showed two distinct peaks in the high-density lipoprotein density range, one of which codistributed with high-density lipoprotein2 and the other with a high-density fraction of high-density lipoprotein3 in the density range of 1.19 to 1.23 gm per ml. The distribution of [3H]taurocholate between albumin and high-density lipoprotein was markedly shifted toward high-density lipoprotein. No [3H]taurocholate association with lipoprotein X was observed. 4. Bilirubin was found to cause a shift of taurocholate from albumin to high-density lipoprotein in vitro. It is proposed that bilirubin is responsible, at least in part, for the observed shift in icteric sera.