The National Cooperative Growth Study has monitored the safety of recombinant human GH (rhGH) since 1985. Data have been collected from more than 19,000 children representing over 47,000 patient-years of rhGH treatment. Children receiving GH for renal disease were more likely to develop problems such as intracranial hypertension than those with GH deficiency (P < 0.01). Children with idiopathic short stature were less likely to develop slipped capital femoral epiphysis than those with GH deficiency or Turner's syndrome (P < 0.01). There was no evidence of an increased recurrence of leukemia or central nervous system tumors. There were 3 new cases of leukemia in children without known risk factors for developing leukemia and 5 cases in children with known risk factors. Growth deceleration associated with high affinity, high capacity antibodies to GH was found in only 2 of 5039 subjects tested (0.04%). Major adverse events in association with rhGH treatment have been rare, and preexisting medical conditions such as renal insufficiency may affect their frequency.