To investigate vessel coagulation depth and tissue damage in therapy with the flashlamp-pumped pulsed dye laser (585 nm, 5 mm spot size, 450 microsecond pulse duration, 6-8 J/cm2), we used the nitroblue-tetrazolium chloride stain in 22 post-treatment biopsy specimens from patients with port wine stain. With this method, thermally damaged tissue can be easily differentiated from unchanged tissue to the level of single cells. The results showed that in superficial port wine stain vessels up to 150 microns in diameter, vessel coagulation was complete and selective without further dermal damage. With the increase of vessel diameter, strong superficial hemoglobin absorption led to only partial vessel-wall coagulation and, in some cases, to superficial dermal damage. Likewise, deeper vessels were not coagulated because of shadow effects by superficial vessel layers. Thus, the overall vessel-wall coagulation depth of the flashlamp-pumped dye laser was limited to a maximum of 0.65 mm (mean 0.37 mm). In addition, some degree of epidermal damage was present in most specimens, which significantly increased with epidermal melanin content and resulted in epidermal coagulation and blistering in pigmented skin. Our results explain the occurrence of crusting, hyperpigmentation, and hypopigmentation in therapy with the flashlamp-pumped dye laser and its limited effect on dark or hypertrophic port wine stains in adults featuring large vessel diameters or multiple vessel layers.