Platelets play a crucial role in the pathophysiology of atherothrombotic disease and are involved in the early thromboembolic phase of ischaemic stroke. Large platelets are known to be more active. We hypothesized that thrombomegaly would be limited to patients with cortical infarction as compared with patients with lacunar infarcts, and that it would be associated with functional outcome. Mean platelet volume (MPV) and platelet count (PC) were studied in 167 hospitalized patients with stroke within 48 h of symptom onset, and 65 age, gender and race matched controls. Stroke was clinically and radiologically sub-typed. MPV was significantly higher in patients with ischaemic stroke than the control group: mean (SD) 7.35 (1.05) vs 7.09 (0.74) fl, 2 P = 0.04; this difference could be explained by MPV being higher in patients with cortical stroke: 7.46 (1.00) fl, 2 P = 0.039, but not lacunar infarction: 7.14 (1.16) fl, 2 P = 1.0. No difference was seen in PC between ischaemic patients and controls: 231 (82) 10(9)/l vs 236 (54) 10(9)/l, 2 P = 0.63. MPV did not change at 3 months post-stroke in surviving patients with ischaemic stroke: 7.39 (1.03) fl vs 7.34 (0.97) fl, 2 P = 0.53. Patients who were dead or dependent at 3 months had a significantly higher baseline MPV and a tendency to a lower PC than those who returned to independence. MPV and PC were not altered in patients with primary intracerebral haemorrhage. No differences in red cell volume was observed. Platelet volume is elevated in acute ischaemic stroke, a finding that persists at 3 months post-stroke and is limited to patients with cortical infarction. Thrombomegaly is a risk factor for a poor outcome after ischaemic stroke.