The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically recalcitrant melasma, solar elastosis, as well as depositional diseases such as mucinosis and amyloidosis.