Rats were fed copper deficient (0.9 microgram/g) or copper-supplemented diets in which the carbohydrate was either starch, sucrose, or fructose (62% by weight) for 7 wk. Regardless of the nature of the carbohydrate, copper deficiency decreased blood ceruloplasmin activity, hepatic copper and ATP levels, and increased plasma cholesterol and triglycerides. Copper deficiency in rats fed sucrose or fructose, but not those fed starch, significantly lowered blood hematocrit, Hb, and albumin and significantly increased heart and liver weight and the glucose response to a glycemic stress. Hepatic copper level was significantly lower in copper-deficient rats fed sucrose or fructose than in those fed starch. Fasting blood glucose, cholesterol, and triglyceride levels were significantly higher in copper deficient rats fed fructose than in those fed starch. During the study 14 copper-deficient rats died, one of 10 fed starch, six of 20 fed sucrose, and seven of 20 fed fructose. Death was apparently the result of rupture of the heart in the region of the apex. These results indicate that fructose-containing carbohydrates as compared to starch markedly increase the severity of copper deficiency in rats. Whether this effect is due to differences in the nature of the simple carbohydrate (fructose versus glucose) or to molecular size (simple versus complex carbohydrate) remains to be established.