Abstract: A method of enhancing the permeability of the skin to an analyte for diagnostic purposes or to a drug for therapeutic purposes is described utilizing microporation and optionally sonic energy and a chemical enhancer. If selected, the sonic energy may be modulated by means of frequency modulation, amplitude modulation, phase modulation, and/or combinations thereof. Microporation is accomplished by (a) ablating the stratum corneum by localized rapid heating of water such that such water is vaporized, thus eroding the cells; (b) puncturing the stratum corneum with a micro-lancet calibrated to form a micropore of up to about 1000 .mu.m in diameter; (c) ablating the stratum corneum by focusing a tightly focused beam of sonic energy onto the stratum corneum; (d) hydraulically puncturing the stratum corneum with a high pressure jet of fluid to form a micropore of up to about 1000 .mu.m in diameter, or (e) puncturing the stratum corneum with short pulses of electricity to form a micropore of up to about 1000 .mu.