Hypovolemia, resulting from blood or water loss, vasoplegia, or a capillary leak, is one of the most common reasons for shock states in the critically ill. Consequently, fluid replacement therapy is one of the cornerstones of the treatment in patients with trauma and/or septic shock. In addition, due to decreased peripheral vascular resistances in combination with altered microvascular blood flow, most frequently the ICU physician is also obliged to use vasoactive drugs in order to control hemodynamics and tissue perfusion. In this context, the question of the adequate perfusion pressure may assume crucial importance. In fact, according to the “two pores” theory for transcapillary fluid exchange, the rate of fluid escape from the vascular into the interstitial space depends on both the hydrostatic capillary pressure and the microvascular permeability [1]. In this issue of Intensive Care Medicine, Dubniks et al.[2] present an interesting article on the effects of increasing mean arterial pressure with iv noradrenaline on plasma volume in a rodent model of increased permeability, induced by injection of dextran 70 in order to obtain an anaphylactic reaction. Plasma volume was measured before and after albumin infusion, and mean arterial pressure was maintained throughout the experiment by noradrenalin infusion to a level above baseline (on average 100 mmHg). The main result was that the increase in blood pressure induced a loss of plasma volume, which was more pronounced in the animals with increased vascular permeability. In previous experiments both in hemorrhaged cats [3] and in rodents with anaphylaxia-related increased permeability similar to the present study [4], the authors’ group had already reported that the relatively poor plasma expansion capacities of various colloid solutions were caused by increased transcapillary leakage due to increased microvascular permeability. In their current study, the authors now demonstrate that the flux of fluids from intravascular to extravascular spaces is, at least in part, driven by the intravascular hydrostatic pressure, and, moreover, that increasing the colloid osmotic pressure fails to compensate this effect.