Concentrations of soluble receptors for tumor necrosis factor (p55 and p75) strongly correlate with clinical stage and progression of infectious diseases, and may be useful in monitoring autoimmune diseases. However, the role of soluble TNF receptors in insulin-dependent diabetes mellitus (type 1 DM) is not clear. We have compared levels of p55 and p75 in sera from different groups of type 1 DM patients. Group 1: 18 patients with type 1 DM duration from 1/2 to 3 years, group 2: 17 patients with type 1 DM duration of more than 10 years, and less than 20 microg/min excretion of albumin in urine, group 3: 24 patients with type 1 DM for more than 10 years and albumin excretion in urine higher than 20 mg/min. Sera from 24 healthy blood donors constituted a control group. We found that patients in group 1 and 2 had lower p55 levels than among controls (20% and 16.7%, respectively, both P < 0.01). Serum levels of p75 did not differ between the groups. Both p55 and p75 increased with severity of type 1 DM complications (P < 0.00001). These results indicate that type 1 DM without complications is associated with lower serum levels of p55 than in healthy controls, and that type 1 DM complications increase the p55 and p75 levels. In addition, the results suggest that increased serum levels of p55 and p75 in type 1 DM patients may be early markers of type 1 DM complications.