To determine the effect of improved, short-term glycemic control on various functions of hemostasis in insulin-dependent diabetes, we measured changes in plasma fibrinogen, fibrinopeptide A (FPA), functional antithrombin III (AT-III), factor VIII:ristocetin cofactor ( VIIIRCoF ), beta-thromboglobulin (BTG), platelet factor 4 (PF4), and platelet aggregation responses to ADP and collagen in 12 patients with low or undetectable stimulated (postprandial) serum C-peptide levels during 4-8 wk (median, 6 wk) of treatment with constant subcutaneous insulin infusion. Mean plasma fibrinogen, FPA, AT-III, VIIIRCoF , and BTG at baseline were elevated compared with normal. Three patients had heightened platelet responses to ADP that did not correlate to other indicators of a hypercoagulable state; the affected patients, in fact, had significantly lower plasma BTG (25.5 +/- 5.3 [SEM] versus 44.6 +/- 4.6 ng/ml, P less than 0.05) and FPA (1.1 +/- 0.1 versus 2.5 +/- 0.5 ng/ml, P less than 0.05) than the remaining patients. Patients with clinically evident vascular disease had higher baseline plasma BTG and FPA than those without vascular disease (44.6 +/- 5.4 versus 30.2 +/- 4.6, and 2.6 +/- 0.6 versus 1.3 +/- 0.2 ng/ml, P less than 0.05, respectively). During treatment, all patients had declining blood glucose (200 +/- 18 to 102 +/- 5 mg/dl, P less than 0.001) and HbA1 (11.8 +/- 0.6 to 10.2 +/- 0.4%, P less than 0.005). No statistically significant changes in hemostatic functions were noted. During treatment, one patient had an acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)