Mean platelet volume (MPV) is increased in patients at high risk for athero-thrombotic diseases. Thus, an elevated MPV may be a risk marker for platelet activation. Healthy subjects with normal triglyceride (TG) levels (90+/-6 mg/dl; n = 40) or mild hypertriglyceridemia (161+/-79 mg/dl; n = 32) were studied. MPV was measured in fasting blood samples before and after stimulation with collagen (10 micro g/ml), and exposure to 4 or 37 degrees C. Samples from the normotriglyceridemic subjects were tested again 4 h after consuming a high-fat drink. Collagen and exposure to 4 degrees C increased MPV, whereas incubation at 37 degrees C lowered MPV regardless of TG level. There was no significant difference in unstimulated MPV between the fasting and the fed states in the normotriglyceridemic subjects (both 7.2+/-0.1 fl; mean+/-SEM), nor between the latter group and hypertriglyceridemic subjects (7.0+/-0.1 fl). There was a significant negative relation between MPV and fasting TG level. This study suggests that MPV response to low-dose collagen may be a useful indicator of platelet propensity to activation. Further studies are warranted to correlate MPV with classical platelet aggregation tests and with the use of platelet-active drugs.