This longitudinal investigation extends our prospective study of the intellectual and academic functioning of children treated for cancer to 4 years after diagnosis. In the longer term, the children who received central nervous system (CNS) chemotherapy experienced greater neurocognitive deficits, particularly in the area of academic achievement, than did the children who did not receive CNS chemotherapy. Specifically, the CNS chemotherapy-treated children scored lower on academic tests of reading at 3 and 4 years after diagnosis. The results suggest that CNS chemotherapy prophylaxis may adversely effect the development of higher-order mental abilities and cognitive skills during the late-effects period and may also impair academic achievement.