Viruses cause asthmatic exacerbations in schoolchildren. We tested the hypothesis that children who wheezed with viral respiratory tract infections secrete higher levels of the type 1 cytokine interferon-gamma (IFN-gamma) in the peripheral circulation than children who had never wheezed. Blood was taken from 13 children (eight atopic) with episodic wheeze and 11 controls. CD4 and CD8 cells were separated from peripheral blood mononuclear cells and stimulated with phorbol 12-myrisate 13-acetate (PMA) and ionomycin for 24 h. IFN-gamma, IL-4, and IL-5 were measured in the supernatant by ELISA. IFN-gamma production by CD4 and CD8 cells was lower in children with a history of wheeze (CD4, P = 0.046; CD8, P = 0.037). These children were then analysed according to atopic status. CD4 and CD8 IFN-gamma production in nonatopic wheezy children was reduced (CD4, P=0.009; CD8, P=0.003). IFN-gamma production by atopic wheezy children was lower than by controls, but the differences were not significant (CD4, P = 0.2831; CD8, P = 0.1372). CD8 IL-5 was lower in children who wheezed (P=0.012). Release of IL-4 and IL-5 by CD4 cells did not differ between the three groups. We propose that defective IFN-gamma secretion by CD4 and CD8 cells may contribute to viral-induced wheeze in nonatopic children.