Pressure sensitive adhesives (PSA) tapes containing different concentrations of lidocaine were prepared by a general casting method using styrene-isoprene-styrene block copolymer, and the in vitro skin permeation of lidocaine from each tape was evaluated using diffusion cell and excised hairless rat skin. The skin permeation was proportionally increased by up to 40% lidocaine in the PSA tape and did not change after this concentration. Although the bending point of the steady-state flux via skin concentration curve was found at 40%, saturated concentration or solubility of lidocaine in the tape was estimated to be about 20% by differential scanning calorimetry (DSC) measurement. In addition, the steady-state flux of lidocaine through skin from water or silicone fluid suspension (92 or 120 micrograms/cm2.h, respectively) was very similar to those of 40, 50 and 60% tapes (105, 101 and 112 micrograms/cm2.h, respectively). Decrease in the concentration in tapes during the permeation experiment explained only part of these phenomena. To analyze them further, the drug free PSA tape with or without (control) skin surface lipid was affixed to 50% lidocaine PSA tape for 48 h, and the amount of lidocaine crystal in the layered tapes was measured by DSC. The amount was found to be lower in the lipid-containing tape than in the lipid-free tape, suggesting that skin surface lipid can dissolve lidocaine crystal or solid in PSA tape to decrease its thermodynamic activity. Thus it is important to follow the concentration and thermodynamic activity of lidocaine in PSA tape, skin and the interface between the two layers to exactly assess its skin permeation flux.