Optimal conditions for extraction of Hypericum perforatum were determined using response surface methodology. A 3 x 4 x 4 full factorial design representing three extraction temperatures, four extraction times, and four solvent concentrations was executed. The overall extraction efficiency was defined by comparing either the total extractable material weight or the individual component peak area to the peak area of luteolin as internal standard. Of the tested variables, the extraction temperature most significantly affected extraction efficiency. Higher temperatures gave better extraction efficiencies, but high temperature also caused decomposition of hypericin. Within the test range, responses for most variables had local maxima. Optimum ranges of time and concentration for individual variables were overlaid. Considering all variables, optimum ranges for extraction time and extraction solvent concentration (percent ethanol in acetone) were 5.0-6.7 h and 44-74% at 23 degrees C, 5.4-6.9 h and 45-72% at 40 degrees C, and 5.3-5.9 h and 44-69% ethanol in acetone at 55 degrees C, respectively.