Degradation of a compound with a hydroxyl group during the course of its diffusion across the skin was investigated. Based on the experimental findings of ashortened retention time of a degradant peak from post-diffusion samples and from the ability to evaporate radioactivity from such samples, it seems that during diffusion the parent compound degrades into a more hydrophilic product which is then oxidized. A tritium label at the carbon with a hydroxyl group was released as a tritiated water. When the post-diffusion samples were left open to the air allowing evaporation of water, there was a corresponding decrease in radioactivity of such samples. There was a linear relationship between the time left open and the fraction of radioactivity lost. When such samples were fractionated by HPLC, and then had their radioactivities measured by scintillation counting, two peaks wre identified. The first peak, which may be attributable to tritiated water, was eluted at the same retention time as the solvent front. The second peak eluted at the retention time of the parent compound. When the evaporation/loss of radioactivity experiment was repeated using a $^{14}C$-labeled compound there was no significant loss of radioactivity, indicating that the earlier loss with $^{3}H$-labeled compound was related to the formation and loas sof tritiated water.