The two basic research tools developed to measure tissue fluid pressure (wick catheter) and osmotic pressure (colloid osmometer) have undergone extensive validation and refinement over the past 20 years. Using these techniques, basic science investigations were undertaken of edema in Amazon reptiles, pressure-volume relations in animals and plants, adaptive physiology of Antarctic penguins and fishes, edema in spawning salmon, tissue fluid balance in humans under normal conditions and during simulated weightlessness, and orthostatic adaptation in a mammal with high and variable blood pressures-the giraffe. Following and sometimes paralleling this basic research have been several clinical applications related to use of our colloid osmometer and wick technique. Applications of the osmometer have included insights into (a) reduced osmotic pressure of sickle-cell hemoglobin with deoxygenation and (b) reduced swelling pressure of human nucleus pulposus with hydration or certain enzymes. Clinical uses of the wick technique have included (a) improvement of diagnosis and treatment of acute and chronic compartment syndromes, (b) elucidation of tissue pressure thresholds for neuromuscular dysfunction, and (c) development of a better tourniquet design for orthopaedics. This article demonstrates that basic research tools open up areas of basic, applied, and clinical research.