During the course of an open immunotherapy (IT) study of ragweed (RW)-allergic patients, nasal mediator release was studied by provocation testing. All subjects had a history of seasonal RW rhinitis, positive skin puncture test to RW, and RW-specific IgE by RAST. Nasal challenge was performed with serial dilutions of RW extract, before and after 12 weekly injections, providing a cumulative dose of 0.22 microgram of Amb a I. Serum IgE and IgG and basophil histamine release with RW were also measured. By 12 weeks of IT, when only 1% of the usual maintenance level dose had been administered, mean histamine release and TAME-esterase activity in nasal washes decreased significantly (p less than 0.05 and p less than 0.01). Prostaglandin D2 release did not change. Skin sensitivity decreased (p less than 0.05), whereas RW-specific IgE increased (p less than 0.05). No significant change in basophil histamine release was observed for RW or a control antigen. Only six of 40 subjects had an RW-specific IgG rise greater than 0.05 microgram/ml. Changes in nasal sensitivity did not correlate with the increases in IgE or IgG or with the change in skin test sensitivity. These present data indicate that there is a significant decline in nasal sensitivity to inhaled RW very early in the course of IT. There is, however, no indication of a relationship between the decreased nasal sensitivity and the production of RW-specific IgG antibodies.