We investigated the comparative effect on long-term growth of CNS prophylactic treatment for acute lymphoblastic leukemia (ALL) with either 25-Gy cranial irradiation or moderate-dose i.v. methotrexate. In 80 children with complete continuous first remission, data on growth and pubertal development were investigated up to 11 y from ALL diagnosis. Forty patients had 25-Gy cranial irradiation, 16 of them with high-risk factors and 24 without. Another 40 non-high-risk ALL patients had moderate-dose methotrexate. Chemotherapy lasted 3 1/4 y for high-risk ALL patients and 2 1/4 y for those not at high risk. Pubertal development and final height were assessed separately for girls diagnosed before or after age 7 and for boys before or after age 9. All patients had a similar decline in height SD score during the first 6 mo of treatment, which persisted in irradiated children only. The nonirradiated group had no further decline. Catch-up growth only started when chemotherapy ended for irradiated and non-irradiated patients alike. Five y after cessation of treatment, changes in height SD score for nonirradiated children remained within the range for healthy children against a significant decline in height SD scores for irradiated children. Pubertal development in irradiated girls diagnosed before age 7 was within normal range, but their final height was disappointing due to a blunted growth spurt. In contrast, irradiated girls diagnosed later had a delayed onset of puberty but satisfactory final height. Comparable results were found in boys.(ABSTRACT TRUNCATED AT 250 WORDS)