2',3'-Dideoxyguanosine (ddGuo) is a potent inhibitor of the human immunodeficiency virus (HIV) in vitro. Because of the potential interest of this compound for the treatment of AIDS, its chemical stability was studied. The degradation of ddGuo in buffers of different pH and ionic strength was followed using LC. A correlation was found between the logarithm of the rate constant of degradation of ddGuo and the ionic strength of the medium, at constant pH. A pH-rate profile was constructed in the acid region using buffers of the same ionic strength. Activation parameters were determined at pH 7.0.