Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long-term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twenty-four patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3-10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2-6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long-term outcome. Full-scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84-133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long-term outcome.