Stereoselective interaction between a chiral nonsteroidal antiinflammatory drug, namely carprofen (CP), and human serum albumin (HSA) was studied, and the results were compared with those obtained with model dyads. In the presence of albumin the same triplet-triplet transition was detected for both CP stereoisomers; however, time-resolved measurements revealed a remarkable stereodifferentiation in the CP/HSA interaction. For each stereoisomer, the decay dynamics evidenced the presence of two components with different lifetimes that can be correlated with complexation of CP to the two possible albumin binding sites (site I and site II). This assignment was confirmed by using ibuprofen, a site II displacer. Thus, the shorter lived components, for which stereodifferentiation was more important (tau(R)/tau(S) ca. 4), were ascribed to the CP triplet state in site I; the lifetime shortening can be attributed to electron-transfer quenching by the only tryptophan (Trp) of the protein. Laser flash photolysis of model dyads containing covalently linked CP and Trp revealed formation of the expected Trp radical cation, providing support for such a mechanism. Moreover, significant stereodifferentiation was observed between the (R)- and (S)-CP-Trp dyads. In the case of CP/HSA complexes, as well as in the model compounds, the stereodifferentiation detected in the decays is in good agreement with that observed in the formation of the only CP photoproduct, resulting from a photodehalogenation process. Moreover, stereodifferentiation was also found to occur for the photobinding of CP to the protein.