INTRODUCTION: Oncolytic viruses preferentially replicate in, and kill cancerous cells. REOLYSIN® is a proprietary isolate of reovirus type 3 Dearing. In two trials using intralesional administration in gliomas and recurrent brain tumours, REOLYSIN® has been well tolerated, with early signs of efficacy. However, intravenous delivery would be easier, cheaper and more acceptable to patients than intralesional administration. This trial aims to identify for the first time whether an oncolytic virus, REOLYSIN®, can cross the blood brain barrier and infect brain tumours following intravenous administration. METHOD: This is an open-label, non-randomised study of intravenous REOLYSIN® administered to patients prior to planned surgery for recurrent high grade glioma or metastatic brain tumours. In total, 12 patients will be treated with a single infusion of 1x10^10 TCID50 of REOLYSIN®. The primary objective is the presence of REOLYSIN® in the resected tumours as assessed by immunohistochemistry, RNA in-situ hybridization and retrieval of infectious virions. RESULTS: Three patients have completed the study to date. All 3 resected patient tumours contained REOLYSIN® RNA and protein. There was evidence for REOLYSIN® productive infection in 2 of the tumours. Grade 3-4 adverse reactions were neutropaenia in 1 patient and lymphopaenia in all 3 patients. CONCLUSION: We have shown for the first time that an oncolytic virus, REOLYSIN®, infects and replicates in brain tumours following intravenous administration. This trial will pave the way for phase I/II trials and combination studies using REOLYSIN® in patients with high grade gliomas and brain metastases.