In 1900 he was sent to Havana as head of an army commission to investigate an outbreak of yellow fever among American soldiers. Following the earlier suggestion by C. J. Finlay that the disease was transmitted by a mosquito vector rather than by direct contact, Reed and his companions used human volunteers under controlled experimental conditions to prove this conclusively. In 1901 they published their findings that yellow fever was caused by a virus borne by the Stegomyia fasciata mosquito (later designated as Aëdes aegypti).
See studies by H. A. Kelly (3d ed. 1923), A. E. Truby (1943), and L. N. Wood (1943).