The purpose of this study was to evaluate the laser-tissue interactions of engineered human skin and <i>in-vivo</i> pig skin following exposure to a single 3.8 micron laser light pulse. The goal of the study was to determine if these tissues shared common histologic features following laser exposure that might prove useful in developing <i>in-vitro</i> and <i>in-vivo</i> experimental models to predict the bioeffects of human laser exposure. The minimum exposure required to produce gross morphologic changes following a four microsecond, pulsed skin exposure for both models was determined. Histology was used to compare the cellular responses of the experimental models following laser exposure. Eighteen engineered skin equivalents (<i>in-vitro</i> model), were exposed to 3.8 micron laser light and the tissue responses compared to equivalent exposures made on five Yorkshire pigs (<i>in-vivo</i> model). Representative biopsies of pig skin were taken for histologic evaluation from various body locations immediately, one hour, and 24 hours following exposure. The pattern of epithelial changes seen following <i>in-vitro</i> laser exposure of the engineered human skin and <i>in-vivo</i> exposure of pig skin indicated a common histologic response for this particular combination of laser parameters.