OBJECTIVE To determine the levels of intraplatelet cGMP, an index of activity of the antiaggregatory nitric oxide pathway, in IDDM patients. RESEARCH DESIGN AND METHODS We measured intraplatelet and plasmatic cGMP levels in 22 IDDM patients and 22 age- and sex-matched control subjects. RESULTS Intraplatelet cGMP levels decreased in the IDDM patients (0.32 ±; 0.16 pmol/109 platelets) when compared with the control group (0.52 ±; 0.32 pmol/109 platelets), P = 0.032. Plasmatic cGMP levels were not significantly different between groups. Intraplatelet cGMP levels correlated negatively with the duration of the disease (r = −0.43, P < 0.05). CONCLUSIONS IDDM patients have lower levels of intraplatelet cGMP, which may be responsible in part for their platelet hyperactivity.