Monitoring of drugs (such as theophylline) with a narrow therapeutic window could be simplified if patients were able to submit blood spots for analysis. This could reduce clinic attendance for venous blood sampling and save staff time. A rapid sensitive method utilizing liquid chromatography-mass spectrometry has been developed to determine the amount of theophylline in blood spots. The lowest level of theophylline analysed in a blood spot was 15 ng extracted into 250 microL and this was still considerably above the limit of quantification (3 ng in 250 microL). The levels of theophylline in blood spots correlated well with theophylline levels in plasma samples obtained from the same patients. The assay might be of use in therapeutic drug monitoring of theophylline and blood spot sampling could be applied to other drugs where therapeutic monitoring is required.