Several defects in immunoregulation have been described in patients with insulin dependent diabetes mellitus (IDDM). We have looked at immunoregulatory T-cell subsets autoantibodies and in vitro IgM production in IDDM patients and their healthy first degree relatives. The proportions of total T-cells (OKT11+), helper/inducer (OKT4+), suppressor/cytotoxic T-cells (OKT8+) and OKT4/OKT8 ratio were normal in 8 patients as well as in their 26 family members and in 40 age-matched controls. Anti islet-cell antibodies (ICA) were found in sera of 6 out of 17 patients (35%) in 1 out of 62 (1.6%) family members and in none of the age-matched healthy controls. A significant increase of in vitro IgM production was found in 8 patients (130 +/- 10 PFC/10(6) cultured cells, mean +/- S.E.) as compared to 21 healthy controls (57 +/- 5.0) (p less than 0.01). In vitro IgM production by B-cells of 22 family members was also increased compared to controls (83 +/- 8.0) (p greater than 0.05). This increased antibody production is characteristic for clinical states associated with impaired immunoregulation, and reflects perturbation of immunoregulatory mechanisms in IDDM.