BACKGROUND. The purpose of the study was to determine the prevalence of metabolic syndrome, growth hormone deficiency, and cardiovascular risk factors among adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with or without cranial irradiation. METHODS. Follow-up was undertaken of 75 randomly selected long-term childhood ALL survivors. Testing included fasting insulin, glucose, lipids, and growth hormone (GH) releasing hormone plus arginine stimulation test. The prevalence of metabolic syndrome was compared with population norms from 1999-2002 National Health and Nutrition Examination Study (NHANES) data, and internally between those with and without past cranial irradiation and those with normal (>16.5 μg/L) versus insufficient (9-16.5 μg/L) versus deficient (<9 μg/L) peak GH secretion. RESULTS. The mean subject age was 30 years and the mean time since ALL diagnosis was 25 years. The prevalence of metabolic syndrome did not differ statistically (P = .87) between study subjects (16.6%) and same-age, same-sex population norms (17.5%). However, 60% of subjects treated with cranial irradiation, compared with 20% of those who were not, had 2 or more of the 5 components of metabolic syndrome. Untreated abnormally low GH was present in 64% of subjects overall and 85% of those who received past cranial irradiation. Cranial irradiation was strongly related to GH deficiency, and in turn lower insulin-like growth factor 1 (IGF-1), higher fasting insulin, abdominal obesity, and dyslipidemia, particularly in women. CONCLUSIONS. Hematologists who treat childhood ALL patients, and particularly those who provide primary care to adult survivors, should be aware of the potential for long-term GH deficiency and adverse cardiovascular and diabetes risk profiles as a consequence of leukemia treatment. © 2006 American Cancer Society.