We examined the sera of 94 subjects with insulindependent diabetes mellitus (IDDM) for the presence of complement-fixing sympathetic ganglia (CF-SG) antibodies. In a cross-sectional analysis (duration 0–43 yr), 22% had detectable CF-SG antibodies. Subjects at high risk for IDDM were also studied. Four groups were studied: group 1 (aged 4–64 yr) islet cell antibodypositive (ICA+) prediabetic subjects, 10 of 19 (53%) were CF-SG+ ; group 2 (aged 6–14 yr) ICA− prediabetic subjects (first-degree relatives of IDDM subjects with either transient hyperglycemia, impaired oral glucose tolerance, and/or first-phase insulin release after intravenous glucose tolerance testing), 4 of 9 (44%) were CF-SG+ (2 of the 4 ICA− CF-SG+ subjects have progressed to IDDM); group 3 (aged 1.5-43 yr) ICA+ IDDM subjects (≤1 yr duration) 6 of 10 (60%) were CF-SG+; and group 4 (aged 8–59 yr) ICA IDDM subjects (≤1 yr duration), 2 of 11 (18%) were CF-SG+. All groups had increased CF-SG compared with controls. Postural blood pressure and simultaneous CF-SG antibody measurements were performed in 28 IDDM subjects. The drop in systolic blood pressure was greater in the CF-SG+ subjects (P < .05), and the frequency of CF-SG was greater in the mean to – 2SD group (P < .03) when data were analyzed within mean ± 2SD of the normal blood pressure response.