The interrelationship between transglutaminases (TGases, EC 2.3.2.13) and silicotic nodule formation in rat lung resulting from experimentally induced silicosis, was studied. The activity of cytosolic TGase C was reduced at the time of silicotic nodule formation, whereas no significant change in the activity of particulate or matrix-associated TGase B associated with an increase in TGase B/TGase C ratios, was found. TGase B may play a role in catalyzing ${gamma}-carboxamide$ crosslinking to fibrosis in the formation of silicotic nodules.