Two high-performance liquid chromatographic (HPLC) techniques have been used for the determination of the lipophilicity of 50 glucocorticosteroids. For a log P range of 1 to 3, we used a persilylated octadecylsilane phase saturated with 1-octanol, which was eluted with 1-octanol saturated phosphate buffer (pH = 7). For log P values greater than or equal to 3.00, the same phase was used without 1-octanol saturation and was eluted with different methanol-buffer mixtures. These two procedures allowed the determination of log P values ranging from 1.00 to greater than 5.00. Good agreement was found between these procedures and others described in the literature. The effect of different structural changes in the glucocorticosteroid molecule on the lipophilicity is discussed.