Argon-fluoride excimer laser ablation of stratum corneum casues deeper tissue damage than expected for thermal or photochemical mechanisms, suggesting that photoacoustic waves have a role in tissue damage. Laser irradiation (193 nm, 14 ns pulses, 1-2 Hz) at two radiant exposures, 60 and 160 mJ/cm2 per pulse was used to ablate the stratum corneum of skin. Light and electron microscopy of immediate biopsies demonstrated damage to fibroblasts as deep as 88 and 220 μm, respectively, below the ablation site. Ablation through water was used to inertially confine the ablation zone. Partial ablation of s.c. through air produced no damage, whereas partial ablation through water damaged skin to a mean depth of 114.5±8.8m (±SD). Full thickness ablation of s.c. through air and water produced damage zones measuring 192.2 ± 16.2 and 293.0 ± 71.6 μm, respectively (p < 0.05). The increased depth of damage in the presence of inertial confinement provided by the layer of water strongly supports a photoacoustic mechanism of damage. The depths of damage for the large spot, line, and small spots were 431 ± 164μm,269 ± 96μm, and no damage. The spot size dependence of the depth of damage is consistent with the geometric attenuation one would expect to be present from a pressure wave related phenomena. Sequential biopsies were taken over a 7 day period for light and transmission electron microscopy. At 24 hours, there was necrosis of the epidermis and papillary dermis subjacent to the ablation site, with neutrophils surrounding and demarcating the affected area. The necrotic zone sloughed by 48 hours. The reepithelialization was complete by 7 days. The sequence of repair is similar to knife wound healing which we have previously studied, and is analogous to other wound healing processes. We have used an experimental model of ArF excimer laser ablation of stratum corneum to investigate laser-induced photoacoustic damage. The evidence for the injury being due to pressure transients is indirect but compelling. Whether these pressure transients are acoustic transients or shock waves has not been determined, although it is our prejudice that shock waves are the predominant force under these conditions. It is important to consider the possible effects of pressure transients in evaluating laser-tissue interactions, particularly when using short pulse, high peak power lasers.