Clinical evaluation of a live orally administered adenovirus 4 vaccine was conducted at the Naval Training Center, Great Lakes, III. In a double-blind epidemiologic investigation the effectiveness of this newer vaccine was compared to that of two other inactivated adenovirus 4 vaccines and appropriate placebos in a population of 2,307 recruits. By detailed clinical examination of all participants requiring hospitalization (644 admissions), syndrome-specific incidences of acute undifferentiated respiratory disease (ARD) and of other respiratory syndromes were derived. Each of the adenovirus vaccines effected a similar 50% to 60% relative reduction of ARD, as well as symptomspecific decreases in the incidence of clinical manifestations of ARD. No evidence of a clinical toxic effect of the live adenovirus vaccine administered orally was detected.