Technical Abstract: A naturally-occurring sesquiterpene, isolongifolenone, derivatives of which have been used extensively as ingredients in the cosmetics industry, was discovered in laboratory bioassays to possess desirable repellent effects against blood-feeding arthropods that vector human diseases such as malaria, West Nile virus, dengue, yellow fever, ehrlichiosis and Lyme disease. We report that (–) isolongifolenone deters the biting of the yellowfever mosquito, Aedes aegypti and Anopheles stephensi, a mosquito vector of malaria, more effectively than the widely used synthetic chemical repellent, Deet. The compound also repelled deer ticks, Ixodes scapularis, and lone star ticks, Amblyomma americanum, as effectively as Deet. Inasmuch as derivatives of isolongifolenone have routinely been used in topically applied cosmetics, we surmise that the compound has good potential for clinical usage as a safe natural-topical repellent to protect humans against blood-feeding arthropods that transmit disease causing organisms.