To produce controlled, spatially confined thermal effects in dermis. A 1 W, 1,500 nm fiber-coupled diode laser was focused with a high numerical aperture (NA) objective to achieve a tight optical focus within the upper dermis of skin held in contact with a glass window. The delivery optics was moved using a computer-controlled translator to generate an array of individual exposure spots. Fresh human facial skin samples were exposed to a range of pulse energies at specific focal depths, and to a range of focal depths at constant pulse energy. Cellular damage was evaluated in frozen sections using nitro-blue tetrazolium chloride (NBTC), a lactate dehydrogenase (LDH) activity stain. Loss of birefringence due to thermal denaturation of collagen was evaluated using cross-polarized light microscopy. The extent of focal thermal injury was compared with a model for photon migration (Monte Carlo Simulation), heat diffusion, and protein denaturation (Arrhenius model). Arrays of confined, microscopic intradermal foci of thermal injury were created. At high NA, epidermal damage was avoided without active cooling. Foci of thermal injury were typically 50-150 microm in diameter, elliptical, and at controllable depths from 0 to 550 microm. Both LDH inactivation and extracellular matrix denaturation were achieved. Spatially confined foci of thermal effects can be achieved by focusing a low-power infrared laser into skin. Size, depth, and density of microscopic, thermal damage foci may be arbitrarily controlled while sparing surrounding tissue. This may offer a new approach for nonablative laser therapy of dermal disorders.