Long-term (5 years) treatment of 20 growth-retarded pre-pubertal children with chronic renal insufficiency (CRI) led to a significant (P < 0.00005) improvement in standardized height from -2.6 at baseline to -0.7 at five years. Eight patients were paused after reaching target height (50th centile midparental height) and 4 (50%) required re-initiation of recombinant human growth hormone (rhGH) because of a substantial decrease in standardized height. Growth potential was not adversely impacted with a delta height age (HA) minus delta bone age (BA) at five years of +0.5 (N = 8). The mean calculated CCr decreased from 32.2 +/- 15.2 ml/min/1.73 m2 at baseline to 24.6 +/- 14.7 ml/min/1.73 m2 at five years (P = 0.04), which would be consistent with the natural history of CRI in children. Despite the absence of clinical consequences, the increase in the mean fasting and two-hour post-prandial plasma insulin levels during treatment compared to baseline requires further investigation. The only clinically significant adverse event potentially related to rhGH was the development of avascular necrosis of the femoral head during the fourth year of treatment in one patient. Long-term rhGH treatment in children with CRI improves the potential of children with CRI achieving target adult height.