RATIONALE: Both secondhand smoke exposure (SHS) and familial atopy are risk factors for asthma; however, studies have been inconsistent regarding an association of atopy with bronchiolitis severity. METHODS: Among 618 mother-child dyads enrolled in the Tennessee Children's Respiratory Initiative at the time of infant acute viral respiratory illness (ARI), 2004-2008, we examined the association of both familial atopy (first degree relative with asthma, allergic rhinitis, or atopic dermatitis) and SHS on severity of infant ARI using an ordinal bronchiolitis severity score (BSS) with higher values indicating more severe disease, and length of hospitalization (LOS) among those hospitalized. Multiple linear regression analysis was used for adjusted effects of SHS and familial atopy on infant outcomes. RESULTS: Demographics of infants exposed to SHS vs. those without SHS included lower birth weight, higher Medicaid enrollment, and less breastfeeding (p < 0.01). In the subset with bronchiolitis (N = 455), infants with SHS had a higher BSS (Median [Interquartile range] 7.0 [4.5,9.0] than infants without SHS 6.0 [IQR: 3.5,8.5], p = 0.016). Among hospitalized infants with familial atopy, those with SHS had an increased LOS compared to those without SHS (3 [2,6] vs. 2.5 [2,4], p = 0.007). There was no difference in LOS by SHS among infants without familial atopy (p = 0.658). CONCLUSIONS: SHS is an important risk factor for infant bronchiolitis severity, and the impact of SHS on bronchiolitis morbidity is greater among infants with familial atopy.