The ability to target genes to the various layers, cell types, and appendages of the skin could be used to correct disorders, including those of aging such as wrinkling, as well as utilize specific cell types for production molecules useful elsewhere in the body. However, the stratum corneum acts as a significant physical barrier to gene transfer into the skin. In this report we describe the ability to target and express the lacZ reporter gene to various depths of the dermis region in hairless mice. Skin-depth targeting is achieved by varying pulsed electrical fields and subsequent pressure from caliper-type electrodes on topically applied naked lacZ gene constructs. With electric pulses and extended pressure, the maximum depth of lacZ expression in the dermis and transfected cells was achieved at 370 micron and 457 cells/mm2, respectively. Gene expression was observed only the hair follicles in the case of the control.