As it was reported earlier, the free propofol percentage is dependent on its total concentration in human blood or plasma protein solution. At total propofol concentrations below 1microgml(-1) the free fraction of the drug increases with the decrease of its total concentration. The results of the experiments performed in Part I indicate that the well-ordered water around a protein molecule (i.e. the hydration layer) is probably the main factor responsible for the mentioned anomalous free drug fraction changes. The experiments carried out in this study with different ligands (homologous saturated fatty acids, indomethacin and lidocaine) show that: 1. ligand hydrophobicity affects the run of the dependence between the free ligand fraction and its total concentration, which confirms the importance of the hydration layer in the drug binding process,2. similar anomalous changes of the free drug fraction are observed not only for drugs interacting with different binding sites on human serum albumin (HSA), i.e. for propofol and indomethacin, but also for basic local anesthetic lidocaine which is known to bind to other plasma protein, alpha-1-acid glycoprotein (AGP).Therefore, the increase of the free drug fraction at its low total concentration does not appear to be an exclusive feature of propofol-HSA system. The results presented in this paper expand the present knowledge about drug-protein binding process and thereby encourage further research on this subject.