Overexpression of heterologous growth hormone (GH) in transgenic mice results in numerous phenotypic effects, including a drastically shortened life span. Early onset of pathological changes in the kidneys, glomerulosclerosis and glomerulonephritis, undoubtedly contributes to and perhaps accounts for reduced longevity of these animals. However, GH-transgenic mice exhibit various symptoms of accelerated aging, including increased astrogliosis, shortened reproductive life span, and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels. The hypothesis that supraphysiological levels of GH can accelerate aging derives indirect support from findings in GH-deficient and GH-resistant mutant mice in which aging is delayed and the life-span is increased and from the reciprocal relationship of body size and longevity within species.