BACKGROUND: At present, there is no rapid method for determining the plasma concentration of i.v. anaesthetics. A solution might be the measurement of the anaesthetic concentration in expired breath and its relation to the plasma concentration. We used chemical ionization methods to determine whether an i.v. anaesthetic can be detected in the low concentrations (parts per billion by volume) in the expired breath of an anaesthetized patient. METHOD: Chemical ionization mass spectrometry can measure trace gases in air with high sensitivity without interference from major gases. We carried out a feasibility trial with a proton transfer reaction mass spectrometer (PTR-MS) to monitor the i.v. anaesthetic agent propofol and two of its metabolites in exhaled gas from an anaesthetic circuit. Exhaled gas was sampled via a 4 m long, unheated tube connected to the PTR-MS. RESULTS: Propofol and its metabolites were monitored in real time in the expired breath of patients undergoing surgery. CONCLUSION: Routine measurement of i.v. agents, analogous to that for volatile anaesthetic agents, may be possible.