Five children had six episodes of central nervous system leukemia which were characterized by features suggestive of hypothalamic infiltration. All five patients had been in prolonged bone marrow remission and had no other evidence of active leukemia when the hypothalamic syndrome was diagnosed. Five of the six episodes responded promptly to intrathecally administered methotrexate and cranial irradiation, but bone marrow relapse, which was resistant to further therapy, developed within 4 months in three patients and after 18 months in the fourth. Only one patient remains in bone marrow remission without recurrence of hypothalamic symptoms 10 months later.