Bilirubin and bile acids may affect erythrocytes. We investigated blood viscosity and erythrocyte structure in patients with cholestatic jaundice ex vivo and studied the short-term effects of bilirubin and bile acids in vitro. Seventeen patients with cholestatic jaundice and controls were studied. Whole-blood viscosity (adjusted hematocrit 45%) at high (94.5 sec(-1)) and low (0.1 sec(-1)) shear rate and plasma viscosity were measured. Erythrocyte structure was assessed in wet preparations of fixed cells. In vitro whole blood was incubated with increasing concentrations of bilirubin (83% conjugated) and bile acids (cholic, lithocholic, deoxycholic, and chenodeoxycholic acid) and the abovementioned investigations were performed. In patients we observed increased whole-blood viscosity at high shear rate (5.82 +/- 0.69 vs 5.04 +/- 0.27 mPa . sec, P = .0001), plasma viscosity (1.48 +/- 0.22 vs. 1.23 +/- 0.07 mPa . sec, P = .0004), and fibrinogen level (4.70 +/- 0.98 g/L vs 2.63 +/- 0.21 g/L, P < 0.001) were observed. The incubation of normal erythrocytes in patients' plasma confirmed an increase in blood viscosity at high shear rate. Erythrocytes from patients with jaundice demonstrated a slight degree of stomatocytic shape transformation (P <.0001). In vitro, bilirubin did not affect erythrocyte shape. Cholic and lithocholic acids caused a slight stomatocytic shape transformation, whereas deoxycholic acid and chenodeoxycholic acid influenced neither blood viscosity nor erythrocyte structure. Patients with cholestatic jaundice have increased whole-blood and plasma viscosity and slightly altered red blood cell shape, possibly the result of a combination of increased levels of bilirubin and bile acids plus an acute-phase reaction.