We have studied 127 children from 5 participating institutions as to the effect of acute lymphoblastic leukemia (ALL) or the therapy used in the treatment of ALL on growth, growth hormone concentrations, and somatomedin activity. The study (SWOG No. 7581) was initiated in December 1975 and was closed to new entry in September 1979 and to data collection in February 1981. Heights, weights, and blood samples for growth hormone and somatomedin activity were obtained at the time of initial diagnosis and at intervals during the 55 months of observation. The percentage of boys less than 4 years of age below the 50th percentile is significantly greater than the expected 50% for both initial and final height (P less than 0.01). Girls less than 4 years appeared to have significantly different percentile height distribution from the normal for their final height measurement (P less than 0.05) but not for their initial height measurement. No other significant differences in the percentile height distribution were found. When growth rate, since time of diagnosis of ALL, is compared to the expected growth of normal children of the same age by linear regression analysis, there is a difference in the slope of the lines. Children with ALL are significantly shorter. The mean initial growth hormone and somatomedin concentration, 6.2 ng/ml and 1.3 micrograms/ml, respectively, vs mean remission growth hormone and somatomedin of 2.5 ng/ml and 1.1 micrograms/ml, respectively, were different. This was significant at P less than 0.01. The slope of the computed regression lines for multiple analysis of growth hormone and somatomedin were negative for more than 60% of the patients when compared to the initial concentration. These data suggest that a significant number of the children less than 4 years of age are short prior to the onset of therapy, and this persists throughout the course of their disease. Second, there is a reduction in growth rate during intensive therapy or the first year of the disease, with a normal growth rate thereafter. Third, growth hormone and somatomedin concentrations appear to be higher at the time of onset of the disease and decrease while on therapy.