The photoreactivity of diastereomeric dyads containing (S)- or (R)-flurbiprofen (FBP) and (S)-Tyr, either directly linked (1) or separated by a cyclic spacer (3) has been investigated. The main feature is a remarkable intramolecular quenching of FBPfluorescence, especially in 1. The process is clearly configuration dependent, being more efficient for the (R,S)- diastereomer in 1 and for the (S,S)- analogue in 3. Noteworthy, exciplex emission is detected in the 380–500 nm region in the case of 3. Fluorescence decay kinetics from the femtosecond to the nanosecond time-domains provides evidence for the dynamic nature of the quenching. In agreement with the steady-state and time-resolved observations, molecular modelling points to a more favourable geometric arrangement of the two interacting chromophores in 1 than in 3.