Commercial quality-control materials and frozen plasma and serum pools were evaluated for high-density lipoprotein (HDL) cholesterol quantitation by the heparin-Mn2+ and phosphotungstate-Mg2+ precipitation methods and by ultracentrifugal and electrophoretic methods. We evaluated among-day precision; inter-method differences in HDL cholesterol quantitation; lipid composition and electrophoretic mobility of th lipoprotein density fractions; and the effects of modifications in reagent concentration and temperature. Frozen plasma pools (in-house) and frozen serum pools (prepared by the Center for Disease Control) were determined to be suitable HDL controls. Also, a commercial lyophilized serum free of very-low-density lipoprotein (VLDL) to which VLDL is added in a diluent solution (Analytical Control) also appeared suitable as an HDL control material. Conventional lyophilized pools (Lyphochek Elevated, Monitrol I, Ortho Normal, Precilip) were less suitable as control materials because of poor between-day precision for one or both of the precipitation methods and, in some cases, because of large absolute differences observed between the HDL methods. A serum pool stabilized with ethylene glycol (Beckman Level I) was the least as appropriate as an HDL control material. Other lyophilized pools--Lipid Fraction Control (Hyland) prepared by a modified lyophilization process and Lipidophor (Immuno Diagnostika) prepared by lyophilization with a stabilizing agent--appear promising.