Newly defined lipophilic indexes, log k', of a series of penicillins and cephalosporins were rapidly and reliably determined by re-versed-phase high-pressure liquid chromatography (HPLC) on bonded octadecylsilane supports. The log k' values obtained from their retention times exhibited a linear relationship with methanol concentration (v/v %) in the mobile phase. The extrapolated log k' values to zero and those at 30% correlated well with the partition coefficients, log P, in 1-octa-nol-water and with Rm values from TLC. This HPLC technique provided some new log P and Rm values for highly ionizable β-lactam antibiotics. The HPLC method for the determination of partition coefficients of drugs has some advantages and is a useful alternative for the determination of log P and Rm.