The effects of ascorbic acid (AsA) and copper on the activity of NADPH-cytochrome c reductase in the liver microsome of guinea pigs were investigated. The enzyme activity was depressed by depletion of AsA. The administration of 500 ppm copper in the drinking water also inhibited the enzyme activity and decreased the amount of AsA in the liver. In the in vitro experiment, 3.8×10^<-6>M of copper inhibited the enzyme activity. The results of these experiments showed that inhibition of the enzyme activity by copper was caused by the direct inhibitory effect of copper ion and also due to the decrease of AsA content.