Fish oil concentrates (Max EPA) were given without other diet modification for eight weeks to five insulin-dependent diabetics and five healthy volunteers, in order to determine their effect on possible in vitro indices of thrombosis. Cholesterol, HDL, LDL, fasting blood sugar, hemoglobin A1c, platelet count, and the osmotic fragility of red blood cells were not significantly changed from baseline values after eight weeks of fish oil consumption. Serum triglyceride levels were lowered by the fish oil (diabetics 130 +/- 23 to 89 +/- 26 mg/dl: normals 107 +/- 16 to 57 +/- 5 mg/dl). Nine out of ten subjects required more arachidonic acid to aggregate their platelets, and six out of ten required more collagen. Whole blood viscosity at low shear rates was increased in diabetics before the fish oil ingestion, and was reduced both in normals and in diabetics after eight weeks of treatment. Before fish oil administration, the diabetics had higher levels of von Willebrand Factor (vWF) (208 +/- 31%) than did controls (117 +/- 26%). There was a statistically significant decrease of serum von Willebrand Factor both in diabetics (p less than 0.01) and in normals (p less than 0.05) after six weeks of treatment. Analysis of the multimeric composition of the vWF indicated that the vWF molecule was not altered. Addition of eicosapentaenoic acid (EPA) or crude fish oil to human umbilical cord endothelial cell cultures did not change vWF levels in the supernatant. Whether these changes in platelet aggregation, whole blood viscosity and vWF can actually be translated into an in vivo amelioration of the vascular complications in diabetes remains to be determined in a carefully controlled clinical trial.