It is not clear why certain infants wheeze during viral upper respiratory tract infections (URTIs) but it is possible that they have a tendency to mount an exaggerated inflammatory response leading to production of mediators that induce airway narrowing. We studied nasal tumour necrosis factor-alpha (TNF alpha) and urinary leukotriene E4 (LTE4) production during infection and after recovery in 31 wheezy infants (median age 6.2 months). Urinary LTE4 production was not altered during wheezy episodes or URTIs. However, the concentration of TNF alpha in nasal lining fluid (NLF) was significantly increased during acute episodes of wheeze compared to recovery (median [interquartile range] of 293 [42-1753] vs 0 [0-203] pg/ml NLF). TNF alpha was detectable more often and in higher concentration when wheezing was due to respiratory syncytial virus. TNF alpha was also present in 7/30 asymptomatic wheezy infants who had recovered from infection (> 100 pg/ml NLF) and in 4/7 non-wheezy siblings during URTIs (> 200 pg/ml NLF). This suggests that upregulation of TNF alpha production is not the only factor that makes some infants wheeze.