Sepsis is characterized by a systemic inflammatory response to a microbial pathogen. In sepsis, capillary permeability is a tightly regulated feature of microcirculation in all organ beds and is fundamentally altered. We investigated the vascular endothelial growth factor (VEGF) level as a vascular permeability factor and the soluble fms-like tyrosine kinase-1 (Flt-1) level as an antagonist of the VEGF receptors. Serum VEGF and soluble Flt-1 levels in 21 patients with septic shock, who were treated with direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), were measured by enzyme-linked immunoassay. The VEGF and the soluble Flt-1 levels were more elevated in patients with septic shock than in controls. Between 14 survivors and 7 non-survivors, there was no significant difference in VEGF level before the DHP-PMX therapy, but the soluble Flt-1 level of survivors was significantly lower than that of non-survivors. Although there was no significant difference between starting and ending VEGF levels in survivors, in non-survivors the VEGF level at the end of DHP-PMX therapy was significantly lower than that at the start. In survivors, the soluble Flt-1 level at the end of DHP-PMX therapy was significantly lower than that at the start. On the other hand, in non-survivors, there was no significant difference between the ending and starting soluble Flt-1 levels. The soluble Flt-1 level may be a suitable marker of disease severity and mortality.