Five previous trials of pulmonary embolism (PE) thrombolysis showed individually that duration of symptoms did not affect lung scan reperfusion or angiographic clot lysis. We conducted an overview of 308 patients from these trials. Using 262 pairs of pre- and postlysis lung scans and 222 pairs of angiograms, we evaluated the relation between duration of PE symptoms and changes in reperfusion and/or clot lysis following thrombolysis. When comparing baseline and 24-hour post-thrombolysis lung scans, 77% of patients overall demonstrated improvement, including 69% who were treated 6 to 14 days after onset of symptoms. We detected an inverse relation between duration of symptoms and improvement on post-treatment lung scan reperfusion scores. For each additional day of symptoms before PE thrombolysis, there was a decrement of 0.8% of lung tissue reperfusion on lung scanning (95% confidence interval [CI], 0.2% to 1.4%, p = 0.008). Adjustment for age and baseline lung scan defect had little effect on the results Similarly, on angiography, less clot lysis immediately following thrombolysis was observed in the group of patients with the longest duration of symptoms compared with those with the shortest symptom duration (mean = 1.0 score unit of angiographic improvement in those with symptoms for > or = 6 days vs 1.7 score units for < or = 1 day of symptoms, p = 0.03). This inverse relation between duration of symptoms and response to thrombolysis indicates that thrombolytic treatment should commence as soon as possible after PE is diagnosed. However, thrombolysis is still useful in patients who have had symptoms for 6 to 14 days.