Embodiments of the invention are directed methods that include a thymidine kinase deficientvaccinia virus. The methods include administering the vaccinia virus at increasedviral concentrations. Further aspects of the invention include methods forinducing oncolysis or collapse of tumor vasculature in a subject having a tumorcomprising administering to a subject administered at least 1 x 108 viral particlesof a TK-deficient, GM-CSF-expressing, replication-competent vaccinia virusvector sufficient to induce oncolysis of cells in the tumor.