During a long-term study in the rat some enzyme activities were determined in plasma, lung, spleen and skeletal muscle. Twelve rats of each sex were investigated every 49 days from 35 until 1115 days of life. Lactate dehydrogenase in lung and spleen decreases; in muscle and plasma, however, the activity varies considerably. Malate dehydrogenase in the tissues remains nearly unchanged apart from distinct peaks in the first year of life; in plasma the activity takes an M-shaped course. In contrast to the changes of glutamate dehydrogenase in the tissues with a tendency to diminish, this enzyme increases in plasma during the lifetime. Aspartate aminotransferase activity in the tissues, except muscle, varies with a rhythmical behaviour, and in plasma shows a gradual increase. Alanine aminotransferase in lung and spleen has two activity peaks. In muscle this enzyme varies only slightly after a steep initial decrease. In plasma the activity has a tendency to rise. Creatine kinase in the tissues reveals several activity peaks. In plasma the activity course is U-shaped. Adenylate kinase in spleen and lung rises, whereas in muscle the activity varies considerably. The nearly identical decrease of alkaline phosphatase activity in the tissues during ageing is also reflected by a concomitant behaviour in plasma. Leucine arylamidase in lung and muscle both have a U-shaped characteristic, whereas in spleen the activity changes in a shorter period. In plasma, a rhythmical behaviour is apparent. Aldolase in plasma tripled during the observation period. Except for lactate dehydrogenase and aldolase, distinct sex-differences are observed in plasma. With progressive age the animals suffer increasingly from characteristic diseases, which beside experimental components have influenced the enzyme pattern. Enzyme activities in plasma and tissues show a complex pattern and are only of limited importance in understanding the ageing process.