The newly introduced Reflotron-HDL-cholesterol determination was compared with conventional precipitation by phosphotungstate/Mg2+ and quantitation of HDL cholesterol in the supernatant by means of the CHOD PAP method. Accuracy and precision were analyzed by means of three different control materials (Precinorm L, Kontrollogen LP, Reflotron-HDL-Precinorm), which were assessed daily in multiple determinations (n = 10 and 5 respectively) for 5 days. In addition, 100 patient samples, (EDTA plasma) which covered a range from 0.35 to 2.50 mmol/l were compared by both methods. The values of the control sera gave a difference of less than 5% from the target values, and the values from the patients' samples showed less than 3% difference between the two methods. The precision within series was always below 6.5%, and the interassay precision below 3.2%. Reflotron-HDL cholesterol determination appears to meet quality requirements on condition that it is performed by well-trained laboratory personnel.