To determine if patients who suffer atherothrombotic ischemic stroke have altered release of tissue plasminogen activator (t-PA), we measured levels in 22 patients within 24 h of onset of symptoms and 1-2 months later. t-PA levels were measured in blood samples by using a colorimetric method after subjecting the plasma to euglobulin fractionation and reacting it with plasminogen and plasmin substrate. Values from a group of normal volunteers previously studied were used as controls. Individual variability in t-PA levels was found acutely and in the recovery phase. During the latter, patients' levels were significantly higher than controls, which was not the case in the acute phase. There was no correlation among t-PA levels, size of cerebral infarct, and patients' clinical status. We propose that endothelial repair and a rebound in endogenous fibrinolytic activity in the absence of peripheral venous disease are responsible for the late (recovery phase) elevation in t-PA.