Three so-called direct and two calculation-based methods were assessed for possible interference of hemolysis, hyperbilirubinemia, and lipemia with the measurement of low-density lipoprotein cholesterol (LDL-C). While neither hemolysis nor hyperbilirubinemia influenced the accuracy of LDL-C measurements, the presence of lipemia variably affected the different methods. In general, calculation-based, indirect methods showed more interference due to lipemia than methods based on "direct" measurements. Further, the analytical interference usually was more related to the type of hyperlipidemia than to the cholesterol and/or triglyceride concentration. On the other hand, even the method based on electrophoretic separation of lipoprotein fractions failed when the triglyceride concentration was extremely high. Recognition of likely interference patterns is important for correct clinical interpretation of LDL-C results obtained by various techniques. Thiocyanate (SCN-) found in serum ordinarily is the metabolite of cyanide that is inhaled with tobacco smoke, ingested with cyanogenic foods, and forms after the administration of certain drugs. We investigated the effect of SCN- on the ionized magnesium and ionized calcium results determined with the AVL and NOVA ion-selective electrodes. We measured SCN concentration in serum from nonsmokers and smokers and found that ionized magnesium results obtained with the NOVA, but not with the AVL, electrode decreased with increasing SCN concentration. The interference by SCN appeared to be equimolar for the NOVA electrode. On the other hand, the ionized calcium results obtained by both methods were unaffected by changes in the SCN- concentration. Thus, the serum SCN commonly found in smokers and, possibly, after ingesting cyanogenic foods and drugs, is expected to cause a clinically significant spurious decrease in the NOVA ionized magnesium results.