This paper reports changes to our previously published high-performance liquid chromatographic method for the measurement of 6-methylmercaptopurine (6-MMP) in red blood cell lysates. The extraction procedure and chromatographic conditions have been improved and the range of the calibration curves has been modified. The recoveries of 10 and 100 ng ml(-1) 6-MMP were 99.0+/-6.0% and 96.3+/-4.0% respectively and the limit of quantification was lowered to 5 ng ml(-1). This method, which does not require radioactive S-adenosyl-L-methionine, is more sensitive, specific and reproducible and may prove useful for routine determination of thiopurine methyltransferase activity in red blood cells.