The feasibility of using cluster secondary ion mass spectrometry for depth profiling of drug delivery systems is explored. The behavior of various biodegradable polymer films under dynamic SF(5)(+) primary ion bombardment was investigated, including several films doped with model drugs. The SF(5)(+) depth profiles obtained from these biodegradable polymer films showed very little degradation in secondary ion signal as a function of increasing primary ion dose, and it was discovered that the characteristic ion signals for the polymers remained constant for ion doses up to approximately 5 x 10(15) ions/cm(2). These results suggest that the polyester structure of the biodegradable polymers studied here allows for a greater ability to depth profile due to ease of main chain scission. Attempts were also made to depth profile through a series of poly(lactic acid) (PLA) films containing varying concentrations of the drug 4-acetamidophenol. The depth profiles obtained from these films show very little decrease in both the 4-acetamidophenol molecular ion and PLA fragment ion signals as a function of increasing SF(5)(+) primary ion dose. Similar results were obtained with theophylline-doped PLA films. These results show that, in some drug delivery devices, it is possible to monitor the distribution of a drug as a function of depth by using cluster primary ion beams.