Infants are at increased risk of developing asthma after acute bronchiolitis. We assessed the hypothesis that cytokine production is related to the development of asthma after bronchiolitis. The smoking history and the presence of atopy or asthma in parents or siblings were recorded and blood mononuclear cell interferon (IFN)-gamma and interleukin (IL)-4 production in response to IL-2 were assessed in 32 infants hospitalized for bronchiolitis and in a subgroup (n = 19) in which pulmonary function tests were performed approximately 4.9 mo later. The presence of asthma was determined by the Delphi consensus method 2 yr after hospitalization. Infants were classified as follows: asthma absent (A, n = 14), possible (Po, n = 9), or probable (Pr, n = 9). Infants with possible and probable asthma had lower IFN-gamma production at the time of bronchiolitis and a trend to lower IFN-gamma production 4.9 mo later when compared with those who had no asthma. At the time of bronchiolitis, IFN-gamma production was: 123 +/- 31 versus 34 +/- 20 versus 21 +/- 14 pg/ml, A versus Po versus Pr (p = 0.02, ANOVA) and 4.9 mo after bronchiolitis, IFN-gamma production was: 147.3 +/- 45 versus 47.4 +/- 30 versus 22.3 +/- 32 pg/ml, No versus Po versus Pr (p = 0.08 ANOVA). IL-4 production did not differ between groups. Infants who went on to develop asthma had more parent smokers (21.4% versus 55. 6% versus 55.6%, A versus Po versus Pr, p < 0.04), lower VmaxFRC (122 +/- 18 versus 77 +/- 7 versus 67 +/- 8% predicted, A versus Po versus Pr, p < 0.02), lower PC40 histamine (6.4 +/- 3.3 versus 1.2 +/- 0.6 mg/ml, A versus Po+Pr, p < 0.03) but no increase in atopy or asthma in their family. Significant positive correlations were found between IFN-gamma production at the time of bronchiolitis and VmaxFRC (r = 0.606) or PC40 histamine (r = 0.648) 4.9 mo after bronchiolitis. Lower IFN-gamma production at the time of bronchiolitis is an indicator of lower pulmonary function and increased responsiveness to histamine 4.9 mo after bronchiolitis and is related to the development of asthma after bronchiolitis in infants.