The implications of multiple viruses and of human bocavirus (HBoV) detection on the presence and severity of respiratory illness is unclear. These questions were evaluated with three studies. The first study was a cross-sectional study of the impact of multiple respiratory virus detections on illness severity in 893 children seeking medical care for respiratory illness. Eighteen percent of virus-positive samples had coinfections. Illnesses with a single virus were more severe, with increased risk of oxygen requirement (p=0.02), extended hospital stays (p=0.002), and admissions to the inpatient (p=0.02) or intensive care units (p=0.04). The second study was a prospective, longitudinal study of the impact of bocavirus on respiratory illness in 119 children under age two attending daycare. Nasal swab samples were collected at enrollment and weekly during respiratory illnesses. HBoV was detected in 70 children (59%) (incidence: 117 HBoV+ illnesses per 100 child-years). Reinfection was observed, with up to 4 separate HBoV+ events documented. Twenty of 45 asymptomatic samples (44%) were HBoV+. HBoV+ illnesses had a longer duration overall (0.9 day increase, 95%C.I.: 0.35, 1.45) and a longer duration of cough (1.1 day increase, 95% C.I.: 0.34, 1.78) compared to HBoV-illnesses. Shedding of HBoV was observed for up to 57 days. These data demonstrate that detection of HBoV in a single respiratory sample is not sufficient to determine the etiology of a respiratory illness. The third study was a case-crossover study of bocavirus detection and disease in 149 children aged 2 to 11 years. Children were tested at their asymptomatic baseline and at respiratory illness, using an established nasal swab assay and a novel saliva assay. HBoV was present in 7 saliva samples taken from 6 children and in only one nasal sample. Five (9%) samples from 56 asymptomatic children ages two to four years were HBoV+. HBoV detection in saliva was not associated with illness (p=0.56). The detection of HBoV in saliva indicates that the virus can be detected outside of the respiratory tract even when no disease is present.