Objectives ‐ Type IV collagen (IV‐C) abnormalities of skin and serum have been reported in patients with amyotrophic lateral sclerosis (ALS). However, there has been no study of urinary IV‐C in ALS. The present study investigates urinary IV‐C and the relation to its skin content in patients with ALS. Material and methods ‐ We studied IV‐C immunoreactivity of skin and measured urinary levels of IV‐C in ALS patients and controls. Results ‐ The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for IV‐C as compared with those of controls. Immunostaining became even weaker as ALS progressed. The urinary level of IV‐C in ALS patients was significantly decreased as compared to diseased controls (P<0.001) and healthy controls (P<0.001), and was negatively and significantly associated with duration of symptoms (r=‐0.85, P<0.001). There was an appreciable positive correlation between urinary IV‐C levels and the density for IV‐C immunoreactivity in ALS patients (r=0.84, P<0.01). Conclusion ‐ These data suggest that a metabolic alteration of IV‐C may occur in ALS patients and decreased levels of urinary IV‐C may be related to the decreased IV‐C immunoreactivity of skin in ALS.