BACKGROUND Isolated lung perfusion (ILuP) is an experimental surgical technique for the treatment of pulmonary metastases. Phase I trials showed a wide range in drug lung levels. This may be due to the variance of lung size and pulmonary intravascular volume (PIV). Therefore, we developed a method to assess PIV and investigated the relation of PIV and dry lung weight (DLW). METHODS Thirty-two rats of 555+/-8 and 199+/-5g underwent left ILuP two, four and eight minutes. Venous effluent was analyzed for haemoglobin, red blood cells (RBC), leucocytes, platelets, albumin and creatinine. PIV was calculated by dividing the product of perfusate volume and post-ILuP parameter by the difference between post-ILuP and pre-ILuP parameter. RESULTS No significant differences in PIV for all perfusion times were noted between the different variables (P=0.14). Based on haemoglobin (P<0.0009), RBC (P=0.006), leucocytes (P=0.0003), platelets (P=0.017) and creatinine (P=0.003) analysis, PIV was significantly smaller in rats of 199g while PIV/DLW ratio was not significantly different. CONCLUSIONS Because PIV/DLW ratio is independent of body weight, we advocate PIV calculation using haemoglobin and RBC as an excellent parameter for drug dose calculation during ILuP intraoperatively in order to achieve more reproducible local drug levels and higher efficacy.