Feverfew (Tanacetum parthenium L., Asteraceae) is a perennial medicinal plant which has been used to alleviate the symptoms of migraines, headaches and rheumatoid arthritis. The herb contains various potentially active constituents such as sesquiterpene-gamma-lactones, flavonoids and volatile oil. The main sesquiterpene-lactone in feverfew is parthenolide which is considered to be responsible for the therapeutical effects. Supercritical CO2 extraction was carried out at different pressures (10-30 MPa), temperatures (40-80 degrees C) and co-solvent contents (0-10% ethanol) in order to study the extraction yield and the parthenolide recovery of the extracts. Leaves collected before and during flowering and flower heads were investigated. A factorial experiment using a full 3(3) design was followed during the experiments and response surface methodology was implemented to analyze the influence of the variables and optimize the extraction. The critical values of parthenolide content were found to be 7% EtOH, 22 MPa and 64 degrees C in case of all three samples. It was determined, that the optimal conditions of the extraction, where the maximum parthenolide content and extract yield can be reached, do not coincide. The highest yield of parthenolide was obtained in the flower heads (0.604 wt.%). (C) 2014 Elsevier B.V. All rights reserved.