Objective: The placebo-controlled, randomized, double-blind study was performed to investigate dose-related effects of oxymetazoline on olfactory function during the course of the spontaneously occurring cold.Methods: Drug effects were assessed using olfactory/trigeminal event-related potentials (ERPs) and psychophysical measures (intensity ratings, odor discrimination, butanol threshold); nasal volume was monitored by means of acoustic rhinometry. The investigation was performed in 36 subjects (mean age 24.6 years). The subjects were assigned to treatment groups A, B or C (three groups with 12 subjects each; six women and six men per group). All the subjects received placebo on the left side; on the right side, group A subjects received placebo and group B and C subjects received 0.25 mg.ml(-1) and 0.5 mg.ml(-1) oxymetazoline, respectively. After onset of the rhinitis (day 0) measurements were performed on days 2, 4, 6 and 35.Results: Oxymetazoline clearly produced an increase in nasal volume. However, during the 2-h observation period, effects produced by the two dosages were not significantly different. Despite the increase in nasal volume, oxymetazoline produced only an increase of the overall intensity of H2S stimuli; it had no systematic effect on other measures of olfactory or trigeminal function. In addition, after all the subjects had recovered from the cold, oxymetazoline had no significant main effect on olfactory/trigeminally mediated sensations.Conclusions: Oxymetazoline appeared to have neither negative nor major positive effects on intranasal chemosensory function. It is hypothesized that oxymetazoline needs to be applied locally to the area of the olfactory cleft in order to significantly improve olfaction during the course of the common cold.