The purpose of this study was to determine the prevalence of thyroperoxidase (TPO) and thyroglobulin (Tg) antibodies, using a sensitive and specific radioimmunoassay method in a large cohort of 254 first-degree relatives of Type 1 diabetic patients with or without other autoimmune endocrinopathy, and to evaluate the predictive value of thyroid antibodies for impaired thyroid function in these groups. TPO and Tg antibodies were found at similar frequencies (12%) in the 254 relatives, and both antibodies were present in 23 cases (9%). Seven subjects displayed subclinical thyroid dysfunction without an abnormal free T4 level. Among first-degree relatives of probands with Type 1 diabetes alone, TPO or Tg antibodies were found in 8 subjects (6%), including 6 with both antibodies. The prevalence of TPO antibodies was significantly greater among relatives of TPO-positive than TPO-negative probands (p < 0.01). In relatives of diabetic patients with other endocrinopathy, frequencies of TPO (20%), Tg (19%) and a combination of both antibodies (15%) were significantly higher than in relatives of Type 1 diabetic patients without endocrinopathy (p < 0.001). TSH levels were abnormal in only one relative of the group without endocrinopathy but occurred in 6 relatives of the proband with overt endocrinopathy-associated diabetes (p < 0.02) in marked association with TPO antibodies (p < 10(-4). It is concluded that relatives of probands with overt endocrine autoimmune disease-associated diabetes, unlike those of probands with diabetes alone, showed increased prevalence of thyroid antibodies and thyroid dysfunction. These results argue for a different risk of thyroid autoimmunity and clinical disease in families of diabetic patients without or with overt endocrine disease. A screening of thyroid autoimmunity is highly recommended for the latter group.