The problem of getting drugs across the so-called blood-brain barrier has long been under extensive investigation; however, the other side of the problem, that of keeping drugs out of the central nervous system (CNS), has not been studied so intently. The role of lipophilicity has long been recognized as being important in CNS penetration by chemicals, but it is believed that not enough attention has been devoted to just exactly what is meant when it is said that 'a lipophilic drug is needed for CNS penetration.' There are other reasons for making drugs hydrophilic. Hydrophobic drugs, other factors being equal, are more inhibitory of biochemical systems than hydrophilic congeners. The report discusses these problems in terms of the octanol-water (log P) hydrophobic scale.