The objective of this study was to compare plasma levels of soluble adhesion molecules and Th1-Th2 type cytokines in 44 children with frequently recurrent respiratory infections (FRRI) of upper airways, defined as having nine or more episodes per year, and in 34 children without recurrence; all subjects were followed-up for 12 mo. The viral etiology was determined by cultures from nasal, pharyngeal, and ear secretions, using PCR and immunofluorescence. Plasma levels of five soluble adhesion molecules (E-selectin, P-selectin, L-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1) and interferon (IFN)-gamma, IL-12, IL-4, and IL-10 were measured in patients and in 15 healthy controls using sandwich ELISA. During acute phase, all patients showed significant increase in plasma levels of soluble adhesion molecules; during the follow-up, the levels were greater in children with FRRI. A difference of cytokine profile was demonstrated between the patients with and without FRRI: an increased IL-4 and IL-10 release with decreased levels of IFN-gamma and IL-12 suggested a skewing into Th2-type response, in patients with FRRI. This pattern persisted during the follow-up. In patients without recurrence, an increased IFN-gamma and IL-12 release, together with decreased levels of IL-4 and IL-10, showed a skewing into Th1-type responses; in the follow-up these cytokines reached normal values. In conclusion, the abnormal levels of all examined parameters in children with FRRI may reflect the persistence of an inflammatory microenvironment in the airways and an activation of the immune system that may contribute to the frequently recurrence of the respiratory disease.