BACKGROUND: The circulation rate and the clinical severity of infections caused by members of the new human rhinovirus C (HRV-C) species remain to be defined. OBJECTIVES: To investigate the epidemiologic and clinical impact of HRV-C strains in a fall outbreak interesting hospitalized patients. STUDY DESIGN: HRV species (A-C) were determined by phylogenetic analysis following amplification of two genome regions (5\'NCR and VP4/VP2) by RT-PCR. HRV species were correlated with age, respiratory tract involvement, clinical symptoms, and HRV load in respiratory secretions. RESULTS: During the first week of the period October-November 2008, single HRV infections were associated with 95% of all respiratory syndromes affecting hospitalized patients. Then, HRV infections (single+coinfections) interested about 90% of positive samples until the end of October, when they declined in frequency until reaching about 30% at the end of November. Overall, 104 HRV strains were detected and, of these, 90 could be classified by phylogenetic analysis, as follows: 45 HRV-A, 12 HRV-B, 28 HRV-C, and 5 human enterovirus D strains. HRV-C identity was confirmed by detection of cis-acting replication elements (cre) in 23/23 strains. As for severity of respiratory syndromes, unlike HRV-A and HRV-B strains, HRV-C strains were responsible for a significantly higher rate (p<0.05) of lower respiratory tract infections in the pediatric as compared to adult patient population. CONCLUSIONS: HRV-C strains have been shown to circulate at a rate intermediate between HRV-A and HRV-B strains, showing a greater degree of clinical severity in the pediatric population.