Background In the acute phase of myocardial infarction (acute MI) marked endothelial damage occurs within the first 24 h following thrombolysis with streptokinase. We investigated whether this is associated with a change in levels of vascular endothelial growth factor (VEGF, possibly marking angiogenesis) in the first 24 h post thrombolysis compared to chronic MI patients (defined as MI > 3 months previously). Methods We recruited 15 patients (nine male, mean age 59 +/- SD 10 years) with first-presentation acute MI, who were given 1.5 million U streptokinase over 1 h and aspirin 300 mg orally as standard treatment. Plasma samples were taken prior to the start of thrombolysis, followed every 15 min for 1 h, at 3 h and finally at 24 h post-thrombolysis. Baseline levels of measured indices in the acute MI patients were compared to two control groups: (i) 26 chronic MI patients (18 male, mean age 59.9 +/- 7.0 years); and (ii) 26 apparently healthy controls (17 male, mean age 59.6 +/- 14.1 years). Plasma VEGF and the soluble form of its receptor Flt-1 (sFlt-1) were measured by ELISA. Results Plasma levels of VEGF were significantly higher in patients with a history of chronic MI compared to patients with acute MI (P=0.007) and healthy controls (P=0.002) with similar levels between acute MI patients and healthy controls (P=0.755). Levels of sFlt-1 in the acute (P=0.013) and chronic (P<0.001) MI groups were lower compared to healthy controls. In the first 24 h post-thrombolysis in the acute MI group, levels of sFlt-1 changed significantly (P=0.039), but there was no change in levels of VEGF (P=0.207). Conclusion In the first 24 h of acute MI, significant changes in levels of VEGF receptor sFlt-1, but not VEGF, are seen. Plasma VEGF and sFlt-1 levels are markedly changed in chronic MI patients, suggesting that the activation of angiogenesis in MI patients may be a delayed response.