Ribonuclease A (RNase A) exhibits a well-defined cold denaturation transition when examined at high pressure (3 kbar) and low temperatures (below -10 degrees C). Our main interest in this study was to investigate the pressure-assisted cold denatured state of RNase A by hydrogen exchange techniques. The protection factors obtained from the kinetic data are similar to those obtained previously for RNase A denatured by exposure to high pressure near its temperature of maximum stability, but differ markedly from those in thermally denatured RNase A. A qualitative analysis of the hydrogen-exchange rates suggests that cold denatured RNase A behaves markedly differently from a random coil, probably due to patches of residual secondary structure.