The purpose of this study was to determine dose effects of n-3 polyunsaturated fatty acids (PUFAs) on mean platelet volume (MPV) and platelet count (PLT-CT) in mildly hypertriglyceridemic subjects. Subjects with a serum triglyceride level between 100 and 300 mg/dL were placed on a corn oil placebo for 4 weeks and then randomly assigned to groups taking seven capsules per day of placebo (n = 47) or one of the following doses of n-3 PUFAs for 20 weeks: 0.5 g (n = 50), 1 g (n = 23), or 2 g (n = 12). At the end of both the placebo period and the treatment period, MPV and PLT-CT were measured without stimulation (baseline 1 following placebo period, baseline 2 following n-3 supplement period) and after ex vivo stimulation with collagen (10 microg/mL), cold (4 degrees C), and heat (37 degrees C). Collagen and cold significantly increased MPV, whereas heat lowered MPV regardless of treatment. All stimuli decreased PLT-CT. Only the 2 g/day dose of n-3 PUFAs increased MPV at baseline 2 (7.2 +/- 0.5 vs. 7.5 +/- 0.5 fL) and after the cold stimulus (7.5 +/- 0.5 vs. 7.8 +/- 0.5 fL). There was no dose-dependent effect of n-3 PUFAs on platelet activation; rather, 2 g of n-3 PUFAs increased MPV slightly in mildly hypertriglyceridemic subjects.