The ability of surface-enhanced Raman spectroscopy (SERS) to measure the chemotherapy drug 5-fluorouracil in saliva is presented. A silver-doped sol–gel provided SERS and also some chemical selectivity. 5-Fluorouracil and physiological thiocyanate produced SERS, whereas large biochemicals, such as enzymes and proteins, did not, supporting the expectation that the larger molecules do not diffuse through the sol–gel to any appreciable extent. In addition, 5-fluorouracil samples of 2 µg ml−1 were easily measured, and an estimated limit of detection of 150 ng ml−1 in 5 min should provide sufficient sensitivity to perform pharmacokinetic studies and to monitor and regulate patient dosage. This would fill a critical need for this highly used drug, since genetic-based variations in its metabolism can range by as much as five-fold from one patient to another. Copyright © 2004 John Wiley & Sons, Ltd.