The dose-response (dose, 0.01, 0.05, 0.1, 0.5, 1, and 5 mg) profiles of 10 atopic and 10 nonatopic subjects were determined for nasal patency, secretion weight, pulmonary function, eustachian tube function, middle-ear function, and symptoms after intranasal inhalation challenges with histamine, bradykinin, methacholine, prostaglandin D2, and prostaglandin F2 alpha (PGF2 alpha). Results demonstrated that challenge with PGF2 alpha increased nasal patency, whereas challenge with all other substances decreased patency. The relationship between substances in eliciting a nasal congestive response was prostaglandin D2 greater than histamine greater than bradykinin greater than methacholine. A similar effect ordering was noted for the postchallenge development of eustachian tube dysfunction. Secretion weights were significantly greater after challenge with histamine compared to all other substances. A decrease in pulmonary function was observed only after challenge with PGF2 alpha, although the effect was not statistically significant. No changes in middle-ear pressure were observed for challenges with any of the substances. Only histamine challenge provoked sneezing, whereas challenge with either of the prostaglandins provoked cough. With the exception of methacholine, all substances caused symptoms of rhinorrhea, congestion, and sore throat. Bradykinin was particularly effective in provoking "pain/pressure"-related symptoms. With the exception of secretion weight, the differences between responses of atopic and nonatopic subjects were not statistically significant. These results document mediator specificity in the physiologic and symptomatic responses to intranasal challenge.