Previous studies have suggested that histamine and leucotrienes (LTs) play an important pathobiological role in IgE-mediated allergic diseases. In vitro studies suggested that an extract of Petasites hybridus (Ze339) blocks LT synthesis in monocytes and granulocytes. Petasins are considered to be the pharmacologically active fraction within Ze339. Patients suffering from allergic rhinitis received two tablets of Ze339 standardised to 8 mg petasins three times a day within a period of 1 week. After 5 days of treatment, Ze339 significantly improved primary endpoints, which were day- and night-time nasal symptoms. Nasal resistance, which was measured by rhinomanometry, gradually decreased as a consequence of Ze339 treatment, reaching normal levels after 5 days (rhinomanometry: from 403.5 ± 62.0 to 844.8 ± 38.8 ml). Levels of inflammatory mediators in nasal fluids and serum were measured 90 min after drug administration every day in the morning. After 5 days of treatment, a significant reduction of histamine and LT levels could be observed. Moreover, quality-of-life scores significantly improved. The drug had no effect on the distribution of lymphocyte subpopulations in the blood or on the capacity of blood leucocytes to generate cytokines and lipid mediators. These results suggest that Ze339 is effective in treating allergic rhinitis patients by decreasing levels of nasal inflammatory mediators.