The incidence of clinical zinc (Zn) deficiency was rare when solutions used for total parenteral nutrition (TPN) contained amino acids derived from hydrolyzed casein or fibrin, inasmuch as the Zn content of these solutions was high. Between 1978 and 1979 at The University of Iowa Hospitals, the incidence of clinical Zn deficiency increased significantly and was noted in eight patients (3%). During this time, the solution used for TPN contained crystalline amino acids and contained lower levels of Zn. The incidence of clinical Zn deficiency apparently decreased in 1980 and 1981, when the TPN solutions were supplemented with Zn intermittently. Only three patients (1%) developed clinical Zn deficiency. The clinical course of these three patients is reported. All three were in a poor nutritional state and had diseases of the gastrointestinal tract or of the pancreas which are known to be associated with decreased absorption and/or excessive loss of Zn from the body. The signs and symptoms of Zn deficiency developed at a time when the nutritional status of the patients was improving. Zinc serum levels were low (15-40 micrograms per deciliter); but none of the three patients had essential fatty acid deficiency. Treatment with intravenous ZnCl2 or oral ZnSO4 caused a rapid and dramatic improvement in the signs and symptoms. Skin lesions disappeared within 8 days after initiation of therapy. It is suggested that in similar patients Zn supplementation should be on a daily basis. Urine, stool, and serum Zn levels should be monitored closely, especially when the nutritional status of the patient is improving.