Human coronavirus (HCoV) is a known cause of influenza-like illness (ILI). In a multi-site, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR-positive for HCoV. The distribution of species was as follows: HCoV-OC43 (34%), HCoV-229E (28%), HCoV-NL63 (22%), and HCoV-HKU1 (16%). We did not observe species-specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV-HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness. This article is protected by copyright. All rights reserved.