The economic impact and medical complication rate of the common cold are well documented, but many of the physiological, inflammatory, and immune responses to common cold viruses have only recently been investigated. The purpose of this study was to compare selected systemic immune and inflammatory responses to experimental rhinovirus (RV)-39 challenge in seronegative allergic rhinitis and non-allergic rhinitis subjects. Peripheral blood was obtained before (baseline), during (acute), and 23 days after (convalescent) RV-39 intranasal challenge and assayed for leucocyte histamine release, serum immunoglobulins, allergen-specific IgE antibodies, plasma histamine, and platelet aggregation. All subjects were infected, as manifested by viral shedding in nasal secretions or seroconversion. RV-39 infection induced significant acute increases in serum IgE, leucocyte histamine release, and platelet aggregation, but caused no changes in serum IgG, serum IgA, serum IgM, and plasma histamine. The first change was confined to the allergic rhinitis subjects. There was no evidence that the acute rise in total serum IgE was due to an elevation of a pre-existing, pollen-specific serum IgE antibody. The results show that intranasal challenge with RV-39 induced changes in systemic immune and inflammatory parameters with a unique response pattern in allergic rhinitis subjects.