The use of different lasers for stimulation in human experimental pain research has provided a sensitive method for evaluation of thin nerve fiber functions. In this study, sensory and pain thresholds were compared to argon-, copper vapour-, Nd:YAG-, and CO2 laser stimulation on hairy skin and on oral mucosa. The influence on thresholds with respect to laser type, stimulation site, surface colour, and stimulus parameters (laser beam diameter and pulse duration) was investigated. Significant differences in thresholds between the four lasers were found on both surfaces; however, no significant differences existed between thresholds on the skin and on the tongue when the same laser was used. The observations imply that wavelength-dependent optical properties of the stimulated tissue influence on threshold determinations. Furthermore, the results indicate that temporal and spatial summation mechanisms may exist for laser induced warmth and pain perceptions. Laser stimulation may be a new tool for the investigation of origin and genesis of various orofacial pain syndromes.