Kahalalide F is a cyclic depsipeptide isolated from the Hawaiian mollusk Elysia rufescens. This compound is under present phase I clinical investigations as an anti-tumor drug. The role of possible metabolic reactions of this drug in (pre-)clinical investigations has not yet been explored. The first results for kahalalide F in this field of research are given in this paper. The chemical degradation of kahalalide F was investigated under acid, neutral and alkaline conditions using high-performance liquid chromatography with ultraviolet detection. The half-lives at 80 degrees C were 1.1, 20 and 8.6 h at pH 0, 1 and 7, respectively. At 26 degrees C and pH 11, the half-life was 1.65 h. At pH 7 and 11, only one reaction product of kahalalide F was observed, kahalalide G, the hydrolyzed lactone product of kahalalide F. At pH 0 and 1, additional reaction products emerged. Metabolic conversion of kahalalide F was tested in vitro using three different enzyme systems based on pooled human microsomes, pooled human plasma and uridine 5'-diphosphoglucuronyl transferase, respectively. The incubated samples were analyzed using the same chromatographic technique as for the degradation samples. Biotransformations were not observed under these conditions and, therefore, it is concluded that kahalalide F is a metabolically stable drug.