St. John's Wort extracts are used for the treatment of mild to moderately severe depression and, their composition and standardization have been thoroughly investigated. Standardization of St. John's Wort extracts has to cope with several factors that affect the phytochemical profile of the plant, with geographic location, seasonal variations and subspecies all being important To. address this issue, three different subspecies of Hypericum perforatum L were profiled in relation to different maturation phases, evaluating the variations in the context of the major secondary metabolites from this plant. HPLC analysis indicated that H. perforatum subs p. perforatum is richer in secondary metabolites than the other subspecies and that the three, subspecies show a different profile during the developmental stages. Hypericins hyperforins, and flavonoids peak at quite different stages, and the standardization of Hyperici extracts based only on the contents of hypericin is not adequate to guarantee batch reproducibility of the extracts. (C) 2009 Elsevier B.V. All rights reserved.