The direct and indirect anti-cell proliferation effects of IFN-alpha produced by BALL-1 cells were examined. Of 23 cell lines, 7 including 2 normal diploids were resistant to a dose 1000 IU/ml of IFN-alpha. On the other hand, 16 cell lines were sensitive and showed IC50 values of less than 1000 IU/ml. This anti-cell proliferation spectrum showed no specificity to tumor origin and its activity was reversible. Cellular oncogene expression was markedly suppressed by IFN-alpha treatment. This finding showed that there might be some correlation between anti-cell proliferation activity and anti-oncogene expression activity. Furthermore, by activating natural killer cell activity and antibody dependent cell-mediated cytotoxicity, IFN-alpha potentiated indirect anti-cell activity.