The persistence of cytoplasmic islet cell antibodies (ICA) more than a year after diagnosis of insulin-dependent diabetes mellitus (IDDM) was investigated in 43 families with at least two children with IDDM. The prevalence of persistent ICA among IDDM patients was 16%. Persistence of ICA appeared to be familial in that siblings with IDDM were significantly more concordant for the presence or for the absence of ICA than expected by chance (P = 0.04). Patients with persistent ICA were older on average at onset of IDDM than patients without persistent ICA after adjusting for duration of disease (P = 0.004). Persistence of ICA was not significantly associated with HLA DR type, immunoglobulin genotype, insulin allele class, sex, history of viral diseases, or prior vaccinations.