Specific damage by selectively absorbed, pulsed lasers can be predicted based on physical models. Thermally mediated alterations can be confined to pigmented targets from the level of subcellular organelles (e.g., mela-nosomes) to large multicellular tissue structures (e.g., blood vessels) by the appropriate manipulation of wavelength and pulse duration. Highly selective damage to human cutaneous microvessels in vivo is shown to occur after 0.3-mus 577-nm dye laser pulses; the epidermis and dermal structures other than vessels are spared. Observations in an animal model suggest that hemorrhage or, at lower doses, selective intravascular coagulation and permanent microvascular hemostasis occur. Highly selective damage to melanized cells and to single melanosomes in situ was shown to occur after single 20-ns 351-nm pulses from a XeF excimer laser. Basal-cell- and melanocyte-specific necrosis is followed by gross hypo-pigmentation. In this case there is no evidence of vascular damage. The most likely modes of selective alterations include localized thermal denaturation, vaporization, and shock-wave generation. Means of predicting and controlling histologically selective radiant heating effects in skin are suggested.