BACKGROUND: Human rhinovirus (HRV) is classified into A, B, and C genogroups. HRVs cause mild upper respiratory infections, but HRV-C was recently found to be a major cause of asthma exacerbation in whites. This study elucidated disease spectrum of HRV infections among Hong Kong children hospitalized with respiratory illnesses. METHODS: This retrospective study recruited 128 children with asthma exacerbations and 192 inpatient controls without allergy and hospitalized for respiratory illnesses within the same week. Their clinical information was retrieved from case records. HRVs in nasopharyngeal aspirates were detected by molecular assays using primers targeting consensus VP4/VP2 coding regions, and their genogroups identified by sequencing. RESULTS: The mean (standard deviation) age of cases and controls was 5.6 (3.6) years and 5.4 (3.8) years, respectively (P = 0.601). HRV was detected in 107 (84.9%) cases and 63 (33.0%) controls (P < 0.0001), and HRV-C in 69.8% and 18.8% of these groups, respectively (P < 0.0001). Detection of HRV-A and -B was similar between these groups (P > 0.15). More subjects with HRV-C needed oxygen supplementation (11.1% vs. 2.6%; P = 0.043). Among controls, HRV infection was associated with acute bronchiolitis (P < 0.001) and bronchitis (P = 0.04), which paralleled those of HRV-C. HRV-A was associated with acute bronchiolitis (P = 0.005). Phylogenetic analysis revealed a diverse group of HRV serotypes (21 for HRV-A, 2 for HRV-B, and 32 for HRV-C). CONCLUSIONS: HRV-C is associated with asthma exacerbation, whereas the presence of all HRVs, or either HRV-A or HRV-C alone, is associated with wheezing respiratory infections in nonasthmatic children. HRV is an important respiratory virus responsible for childhood wheezing illnesses.