Abstract The effect of acute tissue injury on plasma concentrations and urinary excretions of zinc (along with other mono- and divalent cations and renal function) has been followed serially in 10 surgical patients, 10 patients with acute myocardial infarction, and 8 patients with acute suppurative infections. The mean plasma zinc level and standard error of the mean for 204 normal men was 96 ± 1.2 μg per 100 ml. Plasma zinc levels in surgical patients fell from 77 ± 4.7 μg per 100 ml. preoperatively to a low of 53 ± 2.0 μg per 100 ml. 24 hours postoperatively. Thereafter, plasma zinc levels rose steadily to 80 ± 5.5 μg per 100 ml. on the fourth postoperative day. Mean plasma zinc concentrations in the acute myocardial infarction patients fell to a low of 58 ± 3.8 μg per 100 ml. on the second postinfarction day. Striking falls in plasma zinc levels were observed in 2 patients with initial samples obtained within 2 hours after onset of symptoms. Mean plasma zinc levels in patients with acute infections were 65 ± 8.1 μg per 100 ml. at the peak of the infection and 89 ± 7.0 after recovery. Urinary zinc excretions varied widely; it was possible to demonstrate significant increases only in the postoperative patients. These studies indicate that: (1) an acute fall in plasma zinc levels occurs after acute tissue injury regardless of origin; and (2) an effective homeostatic mechanism operates to return plasma zinc levels to a narrow, normal range.