Comparison of the precision and accuracy of measurements made between December 1979 and January 1988 of tricyclic antidepressant drug concentrations in freeze-dried external quality-assurance samples of human serum showed only occasional significant differences between the different chromatographic techniques used for drug assay. Larger differences between data collected in different years correlated with changes in the source of the sample matrix and the personnel responsible for sample preparation. Measurements of amitriptyline and imipramine were more precise than those of nortriptyline and desipramine; the mean coefficients of variation of measurements were 20.2, 19.6, 26.6 and 25.3%, respectively. The data indicate the need for further interlaboratory studies directed at reducing the high level of variability in tricyclic measurements.