By antiapoptotic effects and the induction of the heat-shock response, zinc is supposed to be a promising means of therapy during sepsis. As zinc also stimulates the expression of proinflammatory cytokines, its administration during the proinflammatory stage of septic shock might have adverse effects. Therefore, this study analyzes the influence of zinc during the acute phase of endotoxemia. In a pig model of acute endotoxemia, animals were divided into two groups: group I (n = 5) with saline treatment and group II (n = 5) with zinc treatment in close succession to lipopolysaccharide (LPS) (1.0 mu g/kg Escherichia coli endotoxin WO 111:B4). Hemodynamic and pulmonary monitoring was followed by combined reflection photometry, pulse oxymetry, blood gas samples, and temperature measurement. Plasma concentrations of tumor necrosis factor (TNF)alpha and interleukin (IL)-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). Morphology included the weight of the lungs, the width of the alveolar septae, and the paracentral necrosis rate of the liver. After LPS infusion, group II (zinc) showed an impressive and significant deterioration of all pulmonary and most of the hemodynamical parameters compared to group I (saline). Levels of TNFalpha and IL-6 measured were significantly higher after zinc treatment. In accordance, we found significant more morphologic damages in group II (zinc). The almost simultaneous infusion of zinc and LPS complementary induced proinflammatory effects with a deleterious outcome. The same potentials characterizing zinc as a promising tool of prophylactic therapy in sepsis seem to ban its use during the acute phase.