Outbreaks of adenovirus type 4 (Ad4) acute respiratory disease (ARD) have reemerged among US military personnel during the past decade. A prospective epidemiological investigation of 678 military recruits was conducted at Fort Jackson, South Carolina, in the fall of 1998; 115 (17%) of the recruits were hospitalized for febrile ARD. Adenovirus types 4, 3, and 21 were recovered from the cultures of 70 (72%), 7 (7%), and 2 (2%) of 97 recruits, respectively. In addition, 69 (83%) of the 83 hospitalized and 82 (49%) of the 166 nonhospitalized unit contacts had seroconversion to Ad4, which indicates the very high susceptibility and communicability of Ad4 among military recruits. Young age (<20 years) and male sex increased the risk for anti-Ad4 seroconversion. Recruits from tropical areas had higher preexisting immunity than did recruits from temperate regions. Military recruits are highly susceptible to Ad4 infections. Prompt reinstitution of an adenovirus vaccination program in this high-risk population is urgently needed.