H-1 NMR saturation transfer and T-1 experiments were used to monitor the amide hydrogen exchange rates of 2.5-piperazinedione (diketopiperazine, DKP) and 2-piperidone (delta-valerolactam) in water, Specific acid-catalyzed exchange rate constants (k(H)) for delta-valerolactam and DKP are quite similar, but DKP exhibits an approximately 740-fold larger specific base-catalyzed rate constant (k(OH)) at 25 degrees C, which approaches the diffusion limit, The rate constants for DKP are larger than expected from simple inductive effects. The enhanced rate constants for DKP an attributed to electrostatic interactions involving the second peptide group. In general, the exchange data and inspection of protein structures suggest that such electrostatic interactions may have significant effects on hydrogen exchange in proteins.