The study of the IgE response to seasonal antigen exposure is limited by its occurrence once a year and by the variability of patient exposure to pollens. To overcome these problems, we investigated whether nasal challenge with antigen causes an increase in serum anti-ragweed IgE levels. We challenged individuals with ragweed allergy intranasally with nanogram quantities of ragweed antigen extract and measured their serum anti-ragweed IgE levels before and at weekly intervals after challenge. In a series of studies we found that there was a reproducible rise in antigen-specific serum IgE levels beginning the first week after challenge that plateaued at about 180% of baseline levels during the fourth week and remained elevated for 8 weeks. Not all individuals showed this response. The magnitude of the allergen-specific IgE response to nasal challenge appeared to be greater than the response to seasonal exposure. Treatment with intranasal beclomethasone before challenge did not affect the response. The results demonstrate a human in vivo model for the study of the antigen-specific secondary IgE response to allergen.