Antipyrine-clearance calculated from a single 24 hrs blood sample following i. v. injection of 1 g was determined in insulin dependent diabetics (n = 20), patients with liver cirrhosis (n = 8), with fatty liver + hepatitis (n = 5) and alcoholics with normal liver morphology (n = 3). Antipyrine-clearance values in normal subjects amounted to 58,7 +/- 4,8 ml/min (means +/- s), in cirrhotics to 11,8 +/- 10,1 ml/min (p less than 0.01), in patients with fatty liver to 43,3 +/- 10,1 ml/min (p less than 0.01), and in alcoholics to 62,5 +/- 18,6 ml/min. In diabetics, diseased for many years, also a decrease in the clearance values was seen (41 +/- 17,5 ml/min; p less than 0.05). 15 out of them were below the 2 s range of normal subjects. Thus, the drug-metabolizing capacity in diabetics seems to be markedly reduced, and drug dosage might have to take account of this fact.