OBJECTIVE Vasopressor-induced vasoconstriction may compromise renal and splanchnic blood flow in patients with septic shock, resulting in secondary organ failures. The authors compared the effects of the vasodilatatory agent dopexamine against renal-dose dopamine and placebo in patients with norepinephrine therapy and septic shock, using 24-hour serum creatinine clearance (C(crea)) as a major endpoint. The primary hypothesis to be tested was that dopexamine is more effective than dopamine and that dopamine shows better effects than placebo regarding organ failures and C(crea). METHODS A prospective, randomized, controlled, double-blinded study. METHODS Intensive care unit in a tertiary care university hospital. METHODS Sixty-one patients with septic shock defined according to established criteria. METHODS Patients received either dopexamine (2 microg/kg/min, n = 20), dopamine (3 microg/kg/min, n = 21), or placebo (n = 20). RESULTS The trial groups were similar in terms of baseline characteristics. The authors found no significant differences among the dopexamine, dopamine, and placebo groups with regard to a comprehensive number of renal function parameters including C(crea) and organ-failure scores. There was a significant increase in heart rate after dopexamine infusion; other hemodynamic parameters remained unchanged in the dopexamine group. In a post hoc analysis that included only patients with renal impairment at study inclusion (n = 28), patients who received dopamine showed significant improvements in C(crea) when compared with placebo. Dopexamine was not effective in this subgroup. CONCLUSIONS Dopexamine is no more effective than dopamine or placebo regarding renal function in patients with septic shock requiring norepinephrine. Both therapies do not influence organ-failure scores.