The supercritical fluid extraction behaviors of hyoscyamine and scopolamine were investigated and found to be highly dependent upon the chemical nature of the compounds. Free bases of hyoscyamine and scopolamine were freely soluble in supercritical CO2 with increasing temperature and pressure; however, the salts of these alkaloids were not soluble under any experimental conditions. It was found that alkaline modifiers such as methanol basified with diethylamine could enhance the solubilities and extraction yields of these alkaloids from plant matrices as compared to other modifiers.