Chiasmatic optic glioma is a rare tumor with an erratic natural history, usually seen in young children. A prior study from this institution demonstrated that these lesions were frequently lethal, despite initial clinical stabilization following radiation therapy, and that visual, intellectual, and late endocrinological disabilities were prevalent. A novel approach was developed in 1977, when an initial clinical response to vincristine was recorded in a child with a recurrent optic glioma. Since then, all children with recurrent optic glioma and all children aged 6 years old and under with newly diagnosed optic glioma have been offered a program of initial therapy with vincristine and actinomycin D for six cycles over 18 months. The four children with recurrent tumor who were treated with that regimen remain clinically stable 13 to 115 months after chemotherapy. Twelve children (eight under 24 months old) with newly diagnosed optic glioma have been treated with this program, and three are still on therapy. Four developed progression while on therapy, and five remain stable from 1 to 60 months posttherapy. The four children who developed progressive disease have been treated with radiation therapy and remain stable. Six of the 12 children showed shrinkage of their tumor on computerized tomography while receiving chemotherapy. This program may serve as an alternative to initial radiation therapy in young children.