The aim of the study was to evaluate the efficacy and duration of two doses of dimethindene, in a sustained release pellet formulation, with a standardized grass pollen provocation model (Vienna Challenge Chamber, VCC). The study of 12 grass pollen-allergic volunteers (verified by case history, skin prick test and RAST) was carried out in a placebo-controlled, double-blind, cross-over design. 12 h before a 4-hour continuous challenge with permanent 1,000 Dactylis grass pollen/m3 of air in the VCC, 4 or 8 mg of dimethindene (Fenistil pellets) or an identically appearing placebo was administered in three sessions. Nasal flow and resistance, nasal secretion and subjective symptoms were recorded at 15-min intervals during this long-term challenge under reproducible conditions. In comparison to placebo, dimethindene leads to a statistically significant reduction (p < 0.05) in nasal response and clinical symptoms for at least 16 h after treatment. The efficacy of 8 mg dimethindene was superior to that of 4 mg dimethindene; however, the differences between both active treatments were not statistically significant. Therefore 4 mg dimethindene once a day is adequate for usual pollinotic disease conditions.