Abstract: St. John's Wort products which have enhanced bioactivity in a serotonin re-uptake assay and enhanced stability are identified and manufactured from Hypericum perforatum biomass with supercritical and near critical fluids with and without polar cosolvents. These fluids are used to fractionate the biomass materials in several sequential steps. In each step, the biomass is subjected to a multiplicity of supercritical or near critical fluid extraction steps, with different solvation conditions used for each fraction. Thus, fractionation of the biomass is effected and the St. John's Wort products are manufactured. In addition to excellent overall yield, the bioactivity and stability of the St. John's Wort products manufactured from Hypericum perforatum biomass with supercritical and near critical fluids with and without polar cosolvents are significantly higher than that obtained by conventional organic phase extraction.