Cord serum IgE levels are predictive of subsequent atopic diseases early in life. Lower respiratory illnesses (LRI) have often been included with atopic diseases in infancy but have not been examined as a separate entity for a relation to cord IgE levels. Among 767 healthy newborns in Tucson, Arizona studied longitudinally, cord serum IgE levels were directly related to the subsequent incidence of eczema. In contrast, the incidence of LRI not only failed to show a direct relationship to IgE levels but actually decreased with increasing cord IgE levels from 34.8% in the lowest cord IgE group to 22.2% in the highest IgE group (greater than 1.0 IU/ml IgE; p for trend chi-square less than 0.03). Limiting LRI to those with wheeze did not alter the inverse relationship with IgE levels. The inverse LRI-IgE relationship was strong for non-RSV LRI, whereas RSV LRI had neither a direct nor an inverse relationship. These inverse LRI-IgE relationships were significant for LRI occurring in infants before but not after 6 months of age. Maternal (but not paternal) allergic history was associated with higher cord IgE levels and with an increased incidence of LRI, the latter effect being independent of IgE. This study suggests that most LRI in the first year of life are not early manifestations of an allergic predisposition.