Until recent years, the mouse has been sparsely used in physiological experiments, and therefore data on basic cardiovascular parameters are lacking. Our aim was to get access to interstitial fluid and thereby to study transcapillary fluid dynamics in the mouse. Using a modified wick method, we were able to isolate interstitial fluid from subcutis and skeletal muscle in mice. Three-stranded, dry nylon wicks were inserted post mortem in an attempt to avoid local inflammation and thus, eliminating protein extravasation and wick contamination. COP was measured with a colloid osmometer for sub-microliter samples, and averaged (in mmHg) 18.7 ± 0.4 (means ± SE) in plasma and 9.1 ± 0.4 and 12.3 ± 0.5 in subcutis and muscle, respectively. High performance liquid chromatography of plasma and wick fluid all showed similar patterns, except for some minor peaks eluting in the < 40 kDa region. Plasma protein extravasation as determined by ¹²⁵I-human serum albumin showed that contamination of wick fluid by plasma proteins was negligible (< 2%). Capillary hyperfiltration induced by i.v. infusion of saline (10% of body weight) was reflected in tissue fluid isolated by wicks, as shown by the average postinfusion COP of 14.5 ± 0.6, 6.8 ± 0.3, and 7.7 ± 0.4 mm Hg in plasma, subcutis and muscle, respectively. We conclude that the wick technique can easily be adapted for use in mice, and may represent a reliable method to isolate interstitial fluid and to study transcapillary fluid flux in this species.