The interactions between therapeutic proteins and delivery device surfaces may have a significant impact on the efficacy of a recombinant protein-based biological therapy program. Protein-surface interactions may induce conformational changes and aggregation, resulting in the inactivation of the protein therapeutic and even malfunction of the delivery device itself. Protein adsorption phenomena may compromise the intended therapeutic benefit, drive up dosage levels, and increase treatment costs. We studied the interactions of formulated recombinant interleukin-2 (IL-2) with silicone rubber tubing, a commonly used catheter material, in a recirculating system at 37 degrees C over a 24-h period. Bulk solution protein concentration and bioactivity assays were performed at intervals in order to quantify the impact of time of exposure of the protein to the tubing. Attenuated total reflectance Fourier transform infrared spectroscopy was used to monitor protein conformational changes upon adsorption as well as to quantify protein deposition rates. Adsorption onto the tubing walls resulted in a 7 to 20% reduction in the concentration of IL-2 after 24 h of exposure relative to the initial concentration. At the same time, the residual IL-2 bioactivity levels decreased by 97 to 99.5% of initial activity levels. These activity losses, which far exceed the adsorptive losses, are a direct consequence of the protein-surface interactions. A simple mathematical model was constructed in order to project the impact of IL-2-surface interactions on treatment bioefficacy.