Recent studies have demonstrated that rhinovirus infections can be prevented in the family setting through use of intranasal interferon sprays which are commenced when another family member develops a cold. One hundred and twenty-seven children aged 4-9 years who had been hospitalized during their first year of life for severe infections caused by respiratory syncytial virus were studied virologically and epidemiologically during a seven-month period which included the winter months. The hypothesis was that a significant part of their respiratory morbidity would be preventable by a contact prophylaxis approach using intranasal interferon. However, the findings suggest that a preventive approach of this kind would not substantially reduce the burden of respiratory illness in these children because: the target children themselves more often introduced illness into the family than did other household members; rhinovirus infections preventable by interferon were associated with little lower respiratory morbidity; and rhinoviruses were minor contributors to the total respiratory illness burden in these respiratory illness-prone children.