A quarter of type 1 diabetic patients have thyrogastric autoantibodies (thyroid peroxidase and gastric parietal cell antibodies). Clinical, immune, and genetic risk factors help predict antibody status. First degree relatives of these patients may also frequently exhibit these antibodies. We assessed the prevalence of thyrogastric antibodies and dysfunction in first degree relatives in relation to age, gender, human leukocyte antigen-DQ type, beta-cell antibody (islet cell, glutamic acid decarboxylase-65, and tyrosine phosphatase antibodies), and proband thyrogastric antibody status. Sera from 272 type 1 diabetic patients (116 men and 156 women; mean age, 27 +/- 18 yr; duration, 10 +/- 9 y), 397 first degree relatives (192 men and 205 women; parents/siblings/offspring, 48/222/127; age, 22 +/- 10 yr), and 100 healthy controls were tested for islet cell antibodies and gastric parietal cell antibodies by indirect immunofluorescence and for tyrosine phosphatase, glutamic acid decarboxylase-65, and thyroid peroxidase antibodies by radiobinding assays. Glutamic acid decarboxylase-65 antibodies were present in 68% and 5%, islet cell antibodies were present in 36% and 2.5%, tyrosine phosphatase antibodies were present in 45% and 0.5%, thyroid peroxidase antibodies were present in 21% and 4.5%, and gastric parietal cell antibodies were present in 18% and 11% of diabetic patients and relatives, respectively. The presence of thyroid peroxidase antibodies in relatives was determined by age (beta = 0.22; P = 0.0001) and proband thyroid peroxidase antibodies status (beta = -2.6; P = 0.002; odds ratio = 11.1). Gastric parietal cell antibody positivity in relatives was associated with age (beta = 0.04; P = 0.026). Gastric parietal cell antibody-positive compared with gastric parietal cell antibody-negative relatives were more likely to have gastric parietal cell antibody-positive probands (P = 0.01; odds ratio = 3.0). beta-Cell antibody status and human leukocyte antigen-DQ type did not influence thyrogastric antibody status in relatives. (Sub)clinical dysthyroidism was found in 3%, iron deficiency anemia was present in 12% (26% gastric parietal cell antibody-positive and 9% gastric parietal cell antibody-negative subjects; P = 0.009), and pernicious anemia was found in 0.5% (5% gastric parietal cell antibody-positive and 0% gastric parietal cell antibody-negative subjects; P = 0.012) of relatives. They had less thyroid dysfunction (P < 0.0001) and pernicious anemia (P = 0.018) than diabetic probands. In conclusion, thyrogastric antibodies and dysfunction are more prevalent in type 1 diabetic patients than in first degree relatives. The presence of these antibodies in relatives is associated with age and proband antibody status, but not with beta-cell antibodies or human leukocyte antigen-DQ type.