Changes in rat livers after treatment with phenobarbital (PB), beta- naphtoflavone (beta NF) or 3-methylcholanthrene (MC) was stopped were investigated by biochemical, immunochemical and electron microscopic methods. Repeated injections of each drug led to increases in the relative liver weights, in the microsomal proteins per gram of liver, in the microsomal contents of the total cytochrome P-450, and in the corresponding molecular species of P-450; P-450(PB), when treated with PB and P-450(MC) when treated with either beta NF or MC. After cessation of treatment with PB or beta NF, decreases in all these contents to what were essentially the control values took place approximately in parallel within 7 days. The apparent half lives of cytochrome P-450(PB) and P-450(MC) were calculated from the regression lines of cytochrome P-450 as approximately 15 hours. After treatment with MC, however, all the increases were maintained at approximately the maximal values even after 9 days. Electron microscopy revealed that the smooth ER, which markedly proliferated on PB or beta NF treatment, decreased rapidly after the drug treatment stopped, and was accompanied by an increase in the number of autophagosomes. After treatment with MC, however, the proliferated smooth ER remained even after 9 days.