High-energy light from an argon laser was applied to human oral mucosa in order to investigate regional pain sensitivity. Significant regional differences in sensory and pain thresholds were observed between the test sites on the hard and soft palatal mucosa, the buccal mucosa, the tongue, the lower lip, and the skin on the hand. Pain thresholds were lowest on the tip of the tongue and highest on the hard palate. Sensory and pain thresholds were influenced by different stimulus parameters: pulse duration and laser beam diameter. Blackening of the mucosa in regions with high optical reflectance, such as the hard palate, increased light absorption and, hence, reduced both thresholds significantly. Reflectance spectrophotometric measurements indicated that the hard palatal mucosa reflected argon laser light about 1.5 times more than the tip of the tongue. The different threshold values could, in part, be ascribed to different reflectance and absorption properties of the mucosal areas but also indicated substantial regional variation in pain sensitivity of the human oral mucosa. Measurement of laser thresholds is an appropriate and standardized method for investigating sensory differences in human oral mucosa and may be used to study various pain conditions, e.g., burning mouth syndrome.