In acute quadriplegia we have noted that about one in five patients develops unexplained production of markedly excessive and tenacious bronchial mucus. Spontaneous recovery from mucus hypersecretion usually occurs within weeks to months. Mucus samples collected from 12 patients have been found to be abnormal. Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical ultracentrifuge analysis showed the mucus to contain considerable epithelial glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate compositions were characteristic of the GP from hypersecretory bronchial mucus such as in chronic bronchitis and cystic fibrosis. In five patients studied after recovery from hypersecretion, there tended to be relatively less GP. The mucus samples contained a high density glycoconjugate (GC): this had sugars of GP but also reacted positively with a monoclonal antibody to keratan sulfate. Its amino acid composition was different from that of GP: threonine was lower and glycine was higher than in GP. In mucus from one patient who died, chondroitin sulfate ABC and hyaluronic acid were identified as well. This suggests proteoglycans are involved in the pathophysiology of mucus hypersecretion. The sudden onset and spontaneous recovery of hypersecretion suggests that it is not due to gland hypertrophy. We speculate that in acute quadriplegia it is due to disturbed neuronal control of bronchial mucus gland secretion, perhaps related to initial disappearance and later reappearance of peripheral sympathetic nervous system tone.