Male Wistar weanling rats were divided into three groups and fed one of the following diets for 7, 14 and 28 days: a control diet (21% protein) fed ad libitum, a low protein diet fed ad libitum (the control diet diluted to contain 7% protein by the addition of starch) or an energy and protein restricted diet (control diet fed to provide protein intake equal to that consumed by the low protein group). The activity of glucoronyl transferase was depressed by energy restriction and cytochrome P-450 was depressed by the low protein-ad libitum energy diet compared to controls. In the animals fed the low protein diet with ad libitum energy for 14 or 28 days, the rise in the activity of biphenyl 4-hydroxylase per g liver was sufficient to compensate for the lower liver weight so that the absolute amount of enzyme activity per liver was the same as in the controls. Due to adaptive response of the enzyme to the low protein diet, the activity of biphenyl 4-hydroxylase per g liver was higher than in the controls in animals fed a protein-free diet. It is concluded that the adaptive response of biphenyl 4-hydroxylase was possibly mediated by corticosteroids and was not due to a change in the conformation of the enzyme.