Disseminated intravascular coagulation (DIC) and other clotting abnormalities are common in sick newborn infants who have a variety of conditions. To document evidence of DIC at autopsy, immunoperoxidase staining of fibrin-related antigens (FRA) was used to detect intravascular microthrombi in liver, kidney, and lung from 127 newborns. Patients were selected from seven major disease groups: hyaline membrane disease/bronchopulmonary dysplasia, infection, meconium aspiration, necrotizing enterocolitis, congenital heart disease, other congenital anomalies, and extreme prematurity. Staining for FRA in intravascular microthrombi was seen in 40% of cases studied. The liver showed the highest frequency of intravascular microthrombi, located predominantly in the sinusoids. Unlike the adult kidney, the newborn kidney seldom had evidence of intravascular coagulation. Extravascular staining of FRA was observed in the renal distal tubular epithelium in 48 cases, many of which also had evidence of intravascular FRA staining. No significant differences in FRA staining patterns were seen among the disease groups except for cases of extreme prematurity in which all tissues showed minimal staining. Control tissues from SIDS patients also showed minimal FRA staining. Hepatic sinusoidal staining was the only tissue finding that correlated with thrombocytopenia, a clinical indicator of DIC. Despite the use of this immunohistochemical staining method, discrepancies between the clinical and autopsy diagnosis of DIC remain.