Several studies have shown that respiratory challenge with ovalbumin of mice previously sensitized to this protein causes pulmonary pathology similar to that seen in human asthma, including airway goblet cell hyperplasia which is thought to be caused by upregulation of mucin genes. A recent study of transgenic mice that overexpress murine interleukin-4 in airway cells demonstrated goblet cell hyperplasia in association with pulmonary expression of the Muc-5/5ac but not of the Muc-2 mucin gene. The purpose of this study was to determine which airway mucin genes are involved in the goblet cell hyperplasia seen in mice sensitized and challenged with ovalbumin. Balb/C mice were sensitized (days 0, 4, 7, 11, 14) and challenged (days 25, 26, 27) with ovalbumin (100 micrograms, in saline) (Group A), and studied 24 hours after the last challenge (day 28). Control mice (Group B) were given saline alone. Histological analysis of the lungs revealed a striking lymphocyte and eosinophil inflammatory infiltrate in the interstitium of the bronchovascular bundle and prominent airway goblet cell hyperplasia in Group A but not in Group B mice. Northern analysis of lung RNA demonstrated expression of the Muc-5/5ac gene in Group A but not in group B mice, and expression of the Muc-1 gene in mice from both groups. Our findings demonstrate that pulmonary expression of the Muc-5/5ac mucin gene is associated with airway goblet cell hyperplasia in the ovalbumin murine model of asthma.