Routine calibration of a cholesterol assay system may compromise rather than improve precision. We compared an enzymatic assay on a centrifugal analyzer using a fixed factor with a factor recalculated from the response of standards assayed with each run. Over 36 batch runs, using three quality control materials, we found no statistically significant difference between the two methods in mean value, but in every case the fixed factor values were significantly more precise. With the risk classification system in effect at the time of the study, 32 (9.4%) of 342 patient serum specimens assayed for cholesterol were classified differently based solely on the method of data reduction. Thus, recalibration of our cholesterol assay system contributed to greater imprecision and to discrepancies in classification of patients' risk levels.