We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.