Antibodies to 90 kilodalton (kDa) glycoprotein, a mannose-rich protein of skin and intestinal mucosa, were determined in 31 children or adolescents with untreated celiac disease, in 30 of these patients during gluten withdrawal, and in 17 patients on gluten challenge. Highly elevated antibody levels to 90 kDa glycoprotein were found in patients with untreated celiac disease. Close, positive correlation (r = 0.74, p less than 0.0005) was found between the age of these patients and the level of 90 kDa glycoprotein antibodies. The antibodies to 90 kDa glycoprotein behaved, compared with the reticulin antibodies, in a different manner kinetically. During gluten challenge antibodies to 90 kDa glycoprotein increased on an average 2.6 months later than the antibodies to reticulin. On the other hand, in patients undergoing gluten withdrawal the antibodies to reticulin markedly decreased or disappeared during the first 3 months on the diet, whereas the level of 90 kDa glycoprotein antibodies did not decrease until the 5th to 11th months on the diet. These results suggest that the antibodies reacting with the 90 kDa glycoprotein differ from those reacting with reticulin and that in celiac patients undergoing gluten challenge the synthesis of reticulin antibodies is an earlier event than the production of 90 kDa glycoprotein antibodies. The level of 90 kDa glycoprotein antibodies may reflect the extent of tissue damage.