BACKGROUND It was the aim of the authors to compare all of the latest second-generation antihistamines and to see if there were significant differences in their efficacy. It is important for ENT specialists to know if these differences exist, as it is for general practitioners trying to choose between these drugs. METHODS In 12 confirmed grass pollen allergic patients the authors performed nasal smears to asses eosinophilia, histamine/grass pollen skin tests, and grass pollen nasal provocation tests. All tests were performed before and after administration of one of five different antihistamines (cetirizine, loratadine, ebastine, fexofenadine, mizolastine) or placebo. The order of administration of antihistamines and placebo was randomised, and patients were not aware of which drug they were given. A decrease in nasal eosinophilia (nasal smear), or nasal or skin reactivity (provocation tests) was looked for. RESULTS A significant decrease in nasal eosinophilia was observed for all antihistamines but not for placebo. For the grass pollen nasal provocation tests, the decrease was significant for nasal blockage and sneezing; for rhinorrhea there was an insignificant decrease that was true for all antihistamines. A significant reduction in histamine/grass pollen skin test reactivity was also observed for all antihistamines, during an 8 h observation period. A significant difference in efficacy between the different antihistamines could not be found with any of the tests performed. CONCLUSIONS For the newer nonsedating H1-antagonists there appears to be no clinically relevant differences in activities--at least not in our study. Preference of the patient may be the most important factor in making a choice between these drugs.