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In two patients of meningeal leukemia, the changes of CSF cell pattern following intrathecal methotrexate (MTX) therapy were serially examined by light microscopy. The first case reacted well to cytostatic treatment. 72 h after the first intrathecal MTX injection, an alteration of the chromatin structure could be observed in the nucleus of CSF blast cells; there was a condensation of the heterochromatin, a fragmentation of the nucleus and a dispersal of the chromatin into the cytoplasm. With the therapy-resistant patient No. 2, 72 h after intrathecally administered MTX, the rate of blast cells did not change, and nuclear damage has manifested itself by a rarefaction and disappearance of the chromatin substance. There is strong evidence that these nuclear changes are due to intrathecal MTX treatment. Such changes, however, may not be considered to be specific.