The in vitro/in vivo difference in enhanced skin permeation of nicardipine hydrochloride (NC) by simultaneous use of 1-menthol and ethanol (MEW system, 1-menthol:ethanol:water = 5:40:55) was investigated in hairless rats. First, the cutaneous blood flow clearance (clearance from skin to blood flow) of NC per unit area of skin (CLCB/A), which was comparable to the permeability coefficient across skin (Pc), was calculated from intracutaneous and intravenous injection data using the deconvolution method; the value was 1.67 μ1/h/cm2. Two formulations containing NC and the MEW system, solution (SOL) and 15 % hydroxypropyl cellulose gel (GEL), were used for in vitro and in vivo permeation experiments. The in vitro Pc of NC via excised skin from SOL (23.3 μ1/h/cm2) was significantly higher than CLCB/A, and that from GEL (1.48 μ1/h/cm2) was similar to CLCB/A. Consequently, the steady-state concentration of NC in skin during in vivo application of SOL was 6.6 times higher than corresponding in vitro data. In vivo PcS from SOL and GEL were however significantly lower than CLCB/A. These results may be explained by the findings, using a laser Doppler flowmeter, that cutaneous blood flow was decreased by the application of MEW.