The introduction of the international reference material for serum proteins, CRM 470, has resulted in significant reduction of the among-laboratory variance for most proteins assayed in European national quality assurance programs. In general, the CVs have decreased by 5 to 65%. However, both among- and within-manufacturer variances in many cases remain unacceptably high. In addition, concentration-dependent differences in variance and bias are present for some proteins. Although some variance will persist, reducing variance and bias to levels required for the institution of universal reference ranges will necessitate more accurate transfer of values to calibrants and controls and improved calibration curve fitting by manufacturers, as well as better quality control within laboratories.