Severely malnourished children afflicted by acute lymphoblastic leukemia (ALL), particularly in developing countries, have reduced tolerance to chemotherapy and a compromised prospect for survival. We investigated the prevalence and severity of alterations in growth and nutritional status in children with ALL from population-based referral areas in Canada. All children were treated with Dana-Farber Cancer Institute ALL Consortium protocols. First, the relative impact of cranial irradiation (CI) and chemotherapy on growth was studied in 116 children at diagnosis and at 6-month intervals during treatment. We observed a decline in height standard deviation (SD) score in the first year in all children, and a further decline in height SD score during the second year only in the children who received CI. Weight reduction occurred in the first year, but during the second year there was a disproportionate increase in weight compared with height, suggesting that children treated with ALL have a tendency toward obesity. Both chemotherapy and CI contribute to the altered growth observed in children treated for ALL. Second, intestinal functional integrity was assessed in 16 children during post-induction chemotherapy. Nutrient intake was adequate and there was minimal evidence of malabsorption: fat malabsorption occurred in only 1 child (after treatment-related pancreatitis), abnormal D-xylose absorption occurred in 2 children at 6 months of therapy (returning to normal 6 months later) and abnormal lactose absorption occurred in 4 children. Third, weight, height, whole body lean and fat mass measured by dual-energy X-ray absorptiometry and serum albumin were determined at diagnosis and at 6-month intervals throughout therapy in 19 children with ALL. Height SD scores decreased significantly during treatment. Serum albumin was abnormally low in 6/19 at diagnosis and 14/18 during intensive consolidation therapy. The mean change in the ratio of lean mass to total body weight showed a 5% reduction by 6 months of therapy. Body fat increased from a mean of 22% at diagnosis to 28% at completion of therapy. The majority of children treated for ALL thus have significant changes in nutritional status manifested by reductions in growth, alterations in lean and fat body mass and abnormally low serum proteins during intensive therapy.