Although the number of prescriptions for psychotropic drugs has decreased in recent years, prescriptions for antidepressants are still increasing (Fritze 2002). Hypericum perforatum (St John's wort) is the main psychotherapeutic herbal medicinal product used for treatment of mild-to-moderate depression. The lipophilic constituent hyperforin (2-5% of the extract) demonstrated, similarly to chemical antidepressants, a significant effect on the synaptosomal uptake inhibition of several neurotransmitters in in-vitro assays. In Germany, St John's wort products are distributed via two different markets: products that are pharmacy restricted are only allowed to be distributed in pharmacies; traditionally used products, which do not claim to have a curative character, are allowed to be sold in supermarkets. Depending on the market wherein a St John's wort product is offered, it needs to fulfill the legal requirements regarding pharmaceutical quality, safety and efficacy. Our goal was to compare the quality of St John's wort products distributed in pharmacies with that of those available from supermarkets. Therefore, the quantity of the pharmaceutical active ingredients (the phloroglucinol derivate hyperforin, the flavonoids rutin, hyperoside, isoquercitrin, quercitrin and the biflavonoid biapigenin) was determined by high-performance liquid chromatography (HPLC). The naphthodianthrones hypericines and pseudohypericines were quantified by differential pulse polarography (DPP). The efficacy of the products was investigated by measuring their activity to inhibit serotonin (5-HT) uptake in-vitro using a radio ligand uptake assay. It could be demonstrated that the products were different not only in the concentration of pharmaceutically relevant ingredients but also in showing individual IC50 values (concentration producing half-maximal inhibition) in the serotonin reuptake assay (IC50 values between 3.07 and 17.9 microg extract mL(-1)). The results of our study confirm the assumption that the potency of St John's wort products in inhibiting the uptake of serotonin depends on the amount of hyperforin in their dosage forms. St John's wort products having greater hyperforin content and potency on synaptosomal serotonin uptake inhibition are restricted to be sold only in pharmacies.