The hepatic clearance of many drugs is reduced in the elderly. Contrary to previously held views we suggest the following: 1. Specific activities of several cytochrome P-450 Phase I enzymes are not reduced with age per se in primate and man, nor is enzyme affinity for substrate changed. 2. An important contribution to the reduced hepatic elimination is made by reduction in liver size and blood flow with advancing age. 3. Major changes in liver drug metabolism may occur in frail old people. Future studies of hepatic drug metabolism and ageing must closely define the subject groups under study.