The outcome of patients who show no early response to intravenous (i.v.) tissue plasminogen activator (tPA) therapy is poor. The objective of this study was to evaluate the feasibility of rescue localized intra-arterial thrombolysis (LIT) therapy for acute ischemic stroke patients after an early non-responsive i.v. tPA therapy. Patients with proximal MCA occlusions who were treated by LIT (n = 10) after failure of early response [no improvement or improvement of National Institute of Health Stroke Scale (NIHSS) scores of < or = 3] to i.v. tPA therapy (0.9 mg/kg-10% bolus and 90% i.v. infusion over 60 min) were selected. The recanalization rates, incidence of post-thrombolysis hemorrhage and clinical outcomes [baseline and discharge NIHSS scores, mortality, 3 months Barthel index (BI) and modified Rankin score (mRS)] were evaluated. Rescue LIT therapy was performed on ten MCA occlusion patients (male:female = 3:7, mean age 71 years). The mean time between the initiation of i.v. tPA therapy and the initiation of intra-arterial urokinase (i.a. UK) was 117+/-25.0 min [time to i.v. tPA 137+/-32 min; time to digital subtraction angiography (DSA) 221+/-42 min; time to i.a. UK 260+/-46 min]. The baseline NIHSS scores showed significant improvement at discharge (median from 18 to 6). Symptomatic hemorrhage and, consequent, mortality were noted in 2/10 (20%) patients. Three months good outcome was noted in 4/10 (40%, mRS 0-2) and 3/10 (30%, BI > or = 95). In conclusion, rescue LIT therapy can be considered as a treatment option for patients not showing early response to full dose i.v. tPA therapy. Larger scale studies for further validation of this protocol may be necessary.