The genetic disorders Prader-Willi syndrome and Down syndrome have a number of features in common, for example, both growth and mental retardation. Growth hormone (GH) treatment is becoming part of the clinical management of children with Prader-Willi syndrome, but in children with Down syndrome, such therapy is still on a research level. In this review, we compare the clinical phenotypes of the two syndromes, and report the effects of long-term GH treatment on the linear growth and psychomotor development of 15 young children with Down syndrome (mean age at start of treatment, 7.4 months). The mean height of the treated children with Down syndrome increased significantly from -1.8 to -0.8 SDS (Swedish standard) during the 3 years of GH therapy (P < 0.001). The mean height of a corresponding control group fell from -1.7 to -2.2 SDS. After the cessation of treatment, growth velocity declined in the treated group. Growth of the head did not increase during GH treatment. There was no effect on mental or gross-motor development, although some improvement in fine-motor development was noted in the GH-treated group (P < 0.01). At present, treatment with GH is not recommended in children with Down syndrome who have not been diagnosed with GH deficiency. Long-term studies with an emphasis also on the metabolic effects of GH therapy are necessary before routine treatment can be considered in such children.