Extracts obtained from the dried aerial parts of Clematis species are used as folk remedy worldwide for the treatment of various inflammatory ailments such as rheumatism and to reduce fever. In order to test the effectiveness of extracts, fractions and subfractions from dried Clematis vitalba L. (Ranunculaceae) aerial parts were studied on mice. Extracts are shown to have a potent effect on carrageenan-induced hind paw edema and acetic acid-induced increased vascular permeability models. Through bioassay-guided fractionation procedures a new C-glycosylflavon, 4'-O-coumaroyl-isovitexine (vitalboside) was isolated as the main active ingredient of the aerial parts. Vitalboside showed a potent and dose-dependent (in 75 and 150 mg/kg does, per os) in vivo anti-inflammatory activity against acute (carrageenan-, serotonin- and PGE(2)-induced hind paw edema model, castor oil-induced diarrhea), subacute (subcutaneous air-pouch) and chronic (Freund's complete adjuvant-induced arthritis) models of inflammation. The same compound was also isolated as the main antinociceptive principle which was assessed by using the models based on the inhibition of p-benzoquinone-induced writhings, as well as antipyretic activity against Freund's complete adjuvant-induced increased body temperature. Acute and subchronic toxicity studies were also performed.