The oncolytic effects of encephalomyocarditis (EMC) virus were examined in human retinoblastoma cell (Y79) cultures which were infected with 104tissue culture infectious doses (TCIDs) of the E variant of EMC (EMC-E) virus. The TCIDs were used to titer the maximum effect of EMC virus on L-929 cells. In-vitro studies showed 90% cytopathic effect (CPE) at 24 h and 100% CPE at 52 h. The CPE was used to observe pathologic effects of the cells. In-vivo studies employing human retinoblastoma grown as a tumor in nude mice, revealed degeneration of 80% of the tumor cells at 3 days and total destruction at 4 days following inoculation with the EMC-E virus. The virus is highly neurotropic in mice, but is usually not pathogenic in man. These studies suggest a possible new direction in the treatment of retinoblastoma and other malignant tumors using the viral technology.