Background: Conflicting data exist on the renal effects of hydroxyethyl starch (HES) preparations. The current study evaluates the effects of saline-based 6% HES 130/0.4, 10% HES 200/0.5, and a balanced isotonic crystalloid on renal function and microscopic changes in ovine endotoxemic shock. Methods: Thirty sheep were subjected to endotoxin infusion (Salmonella typhosa) at incremental doses until mean arterial pressure was less than 65 mmHg. Animals were randomized to receive fluid resuscitation with saline-based 6% HES 130/0.4, 10% HES 200/0.5, or a balanced isotonic crystalloid (n = 10 each). Animals surviving the 12-h intervention period were anesthetized and killed. Kidney samples were taken for microscopic analyses. Results: Endotoxemia was associated with hemoconcentration, protein extravasation, and arterial hypotension. Fluid resuscitation established a hypotensive-hyperdynamic circulation with increased cardiac index and oxygen delivery and decreased afterload. Diuresis was lowest in animals treated with 10% HES 200/0.5. In addition, plasma creatinine and urea concentrations increased in sheep treated with 10% HES 200/0.5 (1.2 +/- 0.1 and 19 +/- 2 mg/dl) when compared with the other two groups (0.9 +/- 0.1 and 15 +/- 1 mg/dl, 6% HES 130/0.4; 0.9 +/- 0.1 and 15 +/- 1 mg/dl, crystalloids; each P < 0.05). Electron microscopic tubular injury score was highest in sheep treated with 10% HES 200/0.5 (P < 0.001 vs. 6% HES 130/0.4). Conclusions: In ovine endotoxemic shock, saline-based 10% HES 200/0.5 was linked to impaired renal function and more pronounced tubular epithelial injury when compared with 6% HES 130/0.4 and balanced crystalloids.