The effect of dietary fat on the activity of rat liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase [EC 4.1.1.45] (ACMSD), a key enzyme of tryptophan-niacin metabolism, was investigated. When high-fat diet was given to rats for a week, the activity of ACMSD in the liver was extremely suppressed, but not in the kidney. The liver enzyme activity was correspondingly and constantly reduced half by increasing soybean oil in the diet in 4% stages. The potency of suppression of the enzyme activity in liver was found to be different between soybean oil and lard in diets. Among various dietary fatty acids, saturated fatty acid was observed to be less effective. Unsaturated fatty acids, however, were shown to be suppressive and polyunsaturated fatty acid such as linoleic and linolenic acids more effective than oleic acid in suppressing liver ACMSD activity. These suppressive effects of dietary unsaturated fatty acids on the liver ACMSD activity were not considered to be caused by their direct effect on the enzyme protein. Moreover, neither inhibitor nor activator was thought to be involved in the alteration of the enzyme activity.