The evidence for endothelial dysfunction in sepsis is mostly restricted to animal models. We investigated endothelial function in the skin microcirculation of eight patients hospitalized for septic shock in an intensive care unit (ICU). All patients required adrenergic support. Twelve hemodynamically stable ICU patients without sepsis who did not receive any vasoactive medication were used as controls. The two groups were of similar age and sex ratio. For additional reference, 16 healthy, nonsmoking subjects matched for age and sex to the first two groups were also studied. The evaluation of endothelial function was based on the comparison of skin blood flow responses to iontophoretically applied acetylcholine (Ach, an endothelium-dependent vasodilator) and sodium nitroprusside (SNP, an endothelium-independent vasodilator). Skin blood flow was measured on the volar face of the forearm using laser Doppler imaging. Before application of Ach or SNP, the mean baseline skin blood flow was below 100 perfusion units (PU) in all subjects and did not differ between groups. The maximal increase in blood flow elicited by both agents was significantly depressed in the patients with sepsis (Ach: 167 +/- 63 PU; SNP: 138 +/- 34 PU, mean +/- SD) compared with the ICU control patients (Ach: 291 +/- 135 PU, P < 0.05; SNP: 261 +/- 121 PU, P < 0.01) and the healthy, nonsmoking groups (Ach: 336 +/- 98 PU, P < 0.01; SNP: 304 +/- 81 PU, P < 0.01). The ratio of responses to Ach and SNP did not significantly differ between groups (septic: 1.22 +/- 0.40; ICU control 1.18 +/- 0.46, healthy, nonsmoking 1.12 +/- 0.24, P = 0.86). Thus, sepsis was not associated with a selective depression of the endothelium-dependent response. These results suggest that the capacity of the endothelium to produce signals for vasorelaxation remains intact in the skin microcirculation of patients with septic shock.