Children in a day care center underwent serial nasal lavages in order to assess nasal cytokine expression during acute upper respiratory infections (URI). Interleukin (IL)-l{j, IL-8, IL-6, and tumor necrosis factor-a (TNF-α) were markedly elevated in nasal lavage fluid during acute URI compared to baseline, and all except TNF-α decreased significantly by 2–4 weeks later. Cytokine patterns in respiratory syncytial virus—positive and —negative illnesses did not differ significantly. A subgroup of children also underwent superficial mucosal biopsy under the inferior nasal turbinate. During acute URI, biopsy cells (90%–95% epithelial) showed increased transcripts for IL-lβ, IL-8, and IL-6 in 7 of 9 subjects, suggesting that epithelial cells may be one source of cytokines during acute URI. The results show that inflammatory cytokines are elevated in nasal secretions during acute URI in preschool children. Thus, cytokines are likely to participate in regulation of respiratory virus-induced inflammation.