High density lipoprotein (HDL) infusion and partial plasma exchange were undertaken in two patients homozygous for Tangier disease. Serum samples and ultracentrifugally isolated serum fractions were analysed over a period of 7 days post infusion by agarose electro‐phoresis, two‐dimensional immunoelectrophoresis (employing antibodies to HDL, HDL₃, Apoprotein A‐I, and Apoprotein A‐II), Apoprotein A radioimmuno‐assay, and analytical polyacrylamide electrophoresis. The following observations were made: (a) immediately after HDL substitution the broad‐βband, normally visible upon agarose electrophoresis of Tangier plasma, resolved into a distinct β and pre‐β band; (b) as HDL was cata‐bolized, an abnormal a‐migrating lipoprotein was generated which contained Apoprotein A‐II as protein constituent; and (c) there was a proferential loss of Apoprotein A‐I from HDL and the plasma compartment in the course of HDL catabolism.

The results suggest that the defect in Tangier disease resides with enhanced catabolism or defective synthesis of Apoprotein A‐I.