Catabolism of hyaluronan was studied by injecting hyaluronan (M(r) 200,000) labelled with [125I]-tyramine cellobiose, ([125I]-TC), into the anterior chamber of the rabbit eye. After endocytosis [125I]-TC accumulates in cells, allowing localization of the site of catabolism. When 0.1 ml of the aqueous humour was replaced with an equal volume containing polymer in tracer quantities, 24% was recovered from the eye at 2 hr and 6.5% at 6 hr after injection. With replacement of 0.2 ml of aqueous humour 38% and 19%, respectively, were found within the eye at the same time points. Most of the radioactivity was found in the liver. If the tracer was mixed with Healon the removal from the anterior chamber was delayed. Chromatography on Sephacryl S-300 showed that there was no significant degradation of the labelled polymer in the aqueous humour nor in the remaining parts of the enucleated eye, while most of the tracer extracted from the liver was of low molecular weight. Thus the labelled hyaluronan was being washed out of the eye and subsequently taken up and catabolized by the liver.