We enrolled nine allergic subjects in a double blind, placebo-controlled study to examine the effect of premedication with 0.6 mg of atropine on nasal antigen challenge. The challenge consisted of unilaterally stimulating the nasal septum with diluent followed by three increasing doses of antigen and recording responses bilaterally. Sneezes, symptoms, and nasal airway resistance (NAR) were recorded. Secretions were collected using preweighed filter paper discs and histamine was measured. Antigen challenge with the subjects on placebo led to significant dose-dependent increases in sneezes, symptom scores, ipsilateral and contralateral secretion weights, ipsilateral NAR, and total amount of ipsilateral histamine (p < 0.05 versus diluent). Bilaterally applied atropine led to significant inhibition of ipsilateral and contralateral nasal secretions as well as rhinorrhea scores (p < 0.05 versus placebo) but had no significant effect on other parameters. Challenge after atropine premedication led to higher increases in histamine concentration than placebo (p < 0.01). These results suggest that parasympathetically stimulated fluids did not contain histamine and diluted the histamine released by mast cells. To support this hypothesis, we challenged the same subjects with methacholine. The concentration of histamine decreased and was significantly lower than after challenge with antigen (p < 0.01). The data suggest that: (1) histamine is released locally at the site of antigen challenge, (2) the volume of glandular secretions is primarily controlled by parasympathetic stimulation, and (3) the total amount of a mediator recovered in a fixed time interval best reflects the underlying pathophysiologic events.