Aims: To investigate in a randomized, double-blinded, placebocontrolled, crossover study the effect of a single dose of the nonselective ß-adrenergic receptor antagonist propranolol (40 mg) on hypertonic saline (HS)-evoked masseter muscle pain and autonomic activity during rest and during a mental arithmetic task (Paced Auditory Serial Addition Task, PASAT). Methods: Sixteen healthy women participated in two sessions in which propranolol or placebo was administered orally prior to two 5-minute infusions (30 minutes apart) of HS in the masseter muscle. The second HS infusion was combined with PASAT. HS-evoked pain intensity was scored on a numeric rating scale (NRS, 0 to 10). Heart rate variability and hemodynamic measures were recorded noninvasively (Task Force Monitor). Data were analyzed with repeated measurements analysis of variance (ANOVA). Results: Propranolol did not reduce NRS pain scores compared with placebo but did induce significant autonomic changes with reduced heart rate and increased heart rate variability (standard deviations of all normal RR intervals; root mean square successive differences; low-frequency power; high-frequency power; and total power) independent of the mental task. Conclusion: A single dose of propranolol had no effect on acute HS-evoked pain levels during rest or during mental arousal. However, it influenced the tone of the autonomic nervous system, possibly reflecting an anxiolytic effect. Keywords: autonomic nervous system, experimental muscle pain, mental arithmetic task, propranolol, trigeminal nociceptio