One hundred twenty-five patients were enrolled in a study of growth retarded pre-pubertal (at baseline) children with CRI and were randomized to recieve either rhGH 0.5 mg/kg/day SC or an equal volume of placebo for two years. After two years all patients received rhGH. Treatment was paused in 24 children after reaching mid-parental target height percentile, of whom 17(71%) required re-initiation of rhGH because of a substantial decrease in standardized height. Long-term (5 year) treatment of 35 children led to a significant (p<0.0001) improvement in standardized height from -2.8 at baseline to -0.9 at 5 years. Adult height potential was not adversely impacted with a Δ height age minus Δ bone age at 5 years of +0.3 (N=21). The mean calculated creatinine clearance decreased from 36.2 ± 19.0 mL/min/1.73m2 at baseline to 27.2 ± 18.8 mL/min/1.73m2 at 5 years (p=.0007) which would be consistent with the natural history of CRI children. There was a small increase in the median fasting and 2 hour post-prandial plasma insulin levels during treatment. Development of avascular necrosis of the femoral head, a known compliction of renal osteodystropy was observed in several patients. Presence of AVN was noted on hip x-rays prior to initiation of rhGH in three patients. Because baseline x-rays were not available for most patients this finding requires further investigation. Forty-eight patients had renal transplants and 42 were treated with growth hormone prior to transplant. Thirty patients (23M, 7F) received at least 2 years of rhGH therapy before transplant. Their mean±SD Ht SDS was -2.8± 0.9 at baseline and -1.2 ± 1.2 at transplant. This is a significant (p<0.0001) mean improvement of 1.6 ± 1.0 in Ht SDS after a mean of 4.3 ± 1.7 yr. of rhGH therapy. Long-term rhGH treatment in children with CRI improves the potential of children with CRI achieving target adult height.