Quadriplegic patients have difficulty in clearing lung mucus due to paralysis of muscles of respiration. In about 25% of these patients, excessive mucus in the airway necessitates tracheostomy, and in some patients it is fatal. In others there is spontaneous recovery. To determine if the excessive mucus results from secretion of abnormal mucus or from accumulation of normal mucus, we analyzed the lipids in mucus from eight quadriplegic patients. Lipids were separated from other constituents of the mucus by density gradient ultracentrifugation, extracted with chloroform-methanol (2:1), and examined by high-performance thin-layer chromatography (HPTLC). Cholesterol was the major neutral lipid; phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin were the main phospholipids. Glycolipids were predominant, lactosylceramide (CDH) being the highest in amount. Two-dimensional HPTLC as well as high-performance lipid chromatography also revealed the presence of gangliosides: comparison with standards indicated the presence of GM1, GM2, GM3, and some unidentified gangliosides. In normal mucus, cholesterol is the predominant lipid; phospholipid is present in smaller amounts but glycolipids are not identified. Thus, results of our lipid analysis show that mucus from the quadriplegic patients is abnormal and similar to that in hypersecretory diseases such as chronic bronchitis and cystic fibrosis. Unlike these latter cases, hypersecretion in the quadriplegic has a rapid onset and, often, spontaneous recovery, suggesting that this is due to abnormal stimulation rather than an increase in the population of secretory cells.