Rhinovirus (RV) infections are important triggers of acute asthma symptoms in susceptible persons. To determine whether the presence of allergy is a risk factor for enhanced lower airway effects during RV infection, we experimentally infected (RV16) 18 volunteers with allergic rhinitis and 13 normal control subjects and measured the effects on the response of the lower airways to histamine. All subjects were successfully infected, as indicated by increased upper respiratory symptoms and RV16 cultured from nasal secretions. The change in histamine PD20(deltaPD20) caused by RV infection was significantly different in allergic subjects from that in nonallergic control subjects (deltaPD20 = -0.40 versus -0.03 log units, p = 0.04). This relationship was strengthened after adjusting for initial PD20 and FEV1 (mean deltaPD20 = -0.43 versus 0.01 log units, p < 0.01). The virus-induced deltaPD20 was also influenced by baseline lung function: there was a positive correlation between initial FEV1 and deltaPD20, and a weak but significant negative correlation between baseline PD20 and deltaPD20. These findings indicate that host factors such as allergy, baseline FEV1, and baseline PD20 influence the changes in lower airway physiology caused by RV infection and raise the possibility that these factors contribute to the increased lower airway effects of RV infection in subjects with asthma.