In order to objectively study the histamine sensitivity of the nasal mucosa during 30 days of regular use of oxymetazoline nasal spray (0.5 mg/ml; 0.1 ml in each nostril, thrice daily), eight healthy volunteers were examined with rhinostereometry. After 10 days on being treated, the histamine sensitivity was slightly enhanced. After a further 20 days the sensitivity was significantly increased compared to that before the start of the medication (p < 0.05). This increase in histamine sensitivity for the group is significantly greater than that of healthy drug-free volunteers, and the level is comparable with that of patients with non-allergic nasal hyperreactivity (NANH). It is concluded that a hyperreactive mucosal reaction develops after a relatively short time on oxymetazoline and that the results of this study are in line with the recommendation that the drug should not be used for more than 10 days.