Five compact chemistry analyzers were evaluated for the measurement of lipids. Fresh plasma or serum specimens from a standardized research laboratory were assayed for total cholesterol on all five analyzers. Triglycerides and high-density lipoprotein cholesterol were assayed on the three analyzers that could measure both of these analytes. Study results were interpreted by assessing accuracy and precision and by defining the percentage of patient specimens classified in the same categories as the reference laboratory, according to National Cholesterol Education Program guidelines. Two analyzers met standards for accuracy of cholesterol measurement. Three analyzers met performance standards for precision of cholesterol measurement. Agreement with National Cholesterol Education Program classification of specimens compared with the reference laboratory for total cholesterol ranged from 73% to 96% and was less for indirect low-density lipoprotein cholesterol. We conclude that under controlled conditions, compact chemistry analyzers vary in the reliability of lipid determination and classification of patients.