The purpose of this study was to evaluate whether treatment with interleukin-2 (IL-2) and alpha-interferon (IFN-alpha-2a) causes protein leakage from plasma to the interstitium, leading to the so called 'capillary leak syndrome'. This syndrome is supposed to cause dose-limiting side effects such as weight gain, edema and pleural effusions. Seven patients with disseminated malignant melanoma or renal carcinoma were studied before and after 5 and 12 days of treatment. Transcapillary forces were studied by measuring colloid osmotic pressures in plasma and interstitial fluid (on the thorax and ankle) with a 'wick' method. The colloid osmotic pressure in plasma was reduced by 30-35% during treatment, but with corresponding reductions in the interstitium. Hemoglobin, hematocrit, serum albumin and total protein decreased, whereas moderate edemas and weight gain were observed. These results demonstrate that during treatment with IL-2 and IFN-alpha-2a there are both fluid retention and augmented filtration of fluid from the vascular to the interstitial compartment, but no indication for a capillary leak syndrome. This may explain many of the cardiovascular side effects observed during such treatment.