A new method has been developed for studying interstitial fluid protein concentration: A 3 cm long and 0.5 mm thick nylon thread was sewn into subcutaneous tissue of ether anesthetized rats and left for equilibration with interstitial fluid for 35 to 240 min. The wick was then pulled out, both ends cut off, and the middle part quickly transferred to a tared vial containing 2 ml saline and weighed. Blood-stained wicks, about 1 out of 5, were discarded. After 24 h elution the wick was removed, dried and weighed, allowing calculation of wick fluid volume. Total protein, albumin and hemoglobin concentrations were measured in the eluate. Hemoglobin concentration was less than 0.2 g/100 ml in all but one wick. Implantation of 73 wicks in 24 rats for 35 to 120 min gave an average albumin concentration of 2.10 (S.D. 0.24) g/100 ml, or 63% of plasma albumin concentration. Total protein concentration in 80 wicks averaged 3.44 (S.D. 0.30) g/100 ml, 56% of plasma. The concentrations did not change during this time interval and were reduced by less than 10% by antihistamine/antiserotonin treatment. An irregular rise in concentrations after more than 2 h implantation was delayed by antihistamine/antiserotonin.