Patients with hypertriglyceridemia and mixed hyperlipidemia have been found to have mean plasma viscosities significantly higher than controls (P less than 0.005). In a group of 70 hyperlipidemic patients and controls, plasma viscosity was correlated with plasma triglyceride concentration (r = 0.56, P less than 0.01) and to a lesser extent with the concentration of plasma cholesterol (r = 0.29, P less than 0.05). When isolated lipoprotein fractions were added to lipoprotein-free plasma in increasing concentration over a physiological range, a highly significant linear relationship between plasma viscosity and chylomicron concentrations (r = 0.98, P less than 0.001) was apparent. Furthermore, when chylomicrons were removed by ultracentrifugation, viscosity returned to baseline levels. Added VLDL produced a lesser effect (r = 0.70, P less than 0.001) and added LDL, over the range of cholesterol concentration studied, had no influence on viscosity. These studies indicate that chylomicrons in particular can increase plasma viscosity. Viscosity increases of the magnitude demonstrated may in turn alter blood flow and thus contribute to symptoms such as intermittent claudication. Chylomicron-induced increases in plasma viscosity and subsequent decreases in local pancreatic blood flow may be one of the factors involved in the known relationship between severe chylomicronemia and acute pancreatitis.