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Background Despite the wide application of lasers and electrosurgery in dermatology, the pertinent literature provides conflicting data regarding the lateral thermal injury (LTI) associated with these instruments and its effects on wound healing. This study aims to quantitate the LTI produced by CO2-laser, monopolar electrosurgery (MES), and radiosurgery (MRS) and determine its effects on the healing process (re-epithelialization and inflammatory response) of incisional wounds. Methods Five adult swine of similar weight (22.8-25 kg) were submitted to standardized full-thickness incisions on the lateral abdominal skin by the above instruments (at settings similar to those used in clinical practice) and scalpel (control group). Full-thickness specimens from the surgical site were harvested immediately afterwards and 48 hours later (days 1 and 3). The animals were euthanized by intravenous administration of propofol and pentobarbital. All specimens were formalin fixed, paraffin embedded, cut, and stained with hematoxylin-eosin to quantitate the extent of LTI and inflammatory infiltration. Sections of day 3 were stained with the MIB-1 monoclonal antibody to detect Ki-67 as a marker of epithelial cell proliferation adjacently to the incisions. Results LTI was most extensive in the CO2-laser-group but did not differ significantly between MES- and MRS-groups. Immunohistochemistry ascertained significantly greater epithelial cell proliferation in the CO2-laser-group. Inflammatory infiltration was significantly greater in the CO2-laser-group, when compared with the controls but did not differ significantly between the MES/MRS and control groups. Conclusion CO2 laser incisions exhibit more extensive LTI, epithelial cell proliferation, and inflammatory response. Confirmation of these findings requires a greater sample. [ABSTRACT FROM AUTHOR]