Load-bearing cartilages regularly experience changes in fluid content as the result of changing load. It has been found that these changes in fluid content influence proteoglycan synthesis. The mechanism for this effect is not known. We have measured the influence of changes in cartilage hydration on the [³⁵S]sulphate incorporation rate in both bovine nasal and human articular cartilage in medium whose concentration varied over the range 0.2–2-times physiological strength. In physiological medium the incorporation rate fell in proportion to fluid loss with a 10% fall in cartilage hydration resulting in a 30–50% decrease in ³⁵S-incorporation rates. However, in medium of 0.5-times physiological strength, where the incorporation rate was only 40% of control values, the incorporation rate increased initially rather than falling as the cartilage lost fluid. These changes in hydration and hence proteoglycan content resulted in changes in the extracellular ionic composition of cartilage. When this was monitored in terms of [Na⁺]_c, the internal sodium concentration, as a marker for changes in cartilage ionic composition, we found that incorporation rate varied with [Na⁺]_c rather than directly with hydration.