The caffeic acid content of storage root periderm and cortex tissues of genetically diverse sweet potato [Ipomoea batatas (L.) Lam.] cultivars and breeding clones was quantified by high-performance liquid chromatography. Periderm caffeic acid content of the clones ranged from 0.008 to 7.97 mg/g dry weight, whereas the highest cortex content was 0.047 mg/g. Clones varied greatly in periderm caffeic acid content in all experiments, but there were also differences between experiments in content averaged for all clones. This indicates that periderm caffeic acid content is subject to genetic and environmental influences. Caffeic acid inhibited the growth of four sweet potato pathogenic fungi and germination of proso millet seeds in bioassays. Inhibitory activity in the bioassays suggests that high periderm caffeic acid levels contribute to the storage root defense chemistry of some sweet potato genotypes.