An accurate RP-HPLC method for the quantitative determination of two water-soluble biologically active compounds, salidroside (p-hydroxyphenethyl-beta-D-glucoside) and specnuezhenide in the fruits of Ligustrum lucidum Ait (a crude drug in Chinese traditional medicine) was developed. The reversed-phase column was Nova-Pak C18, saturated with water before the injection of the samples and eluted with a mobile phase of methanol:water (4:6, v/v). The detection wavelength was 230 nm. The recoveries of the two compounds were 96.1 and 97.0%, respectively. The contents of salidroside and specnuezhenide in the fruits of Ligustrum lucidum Ait and two traditional Chinese patent medicines in which this crude drug was an important component, Erzhi Pills and Anshenbuxin Pills, were determined.