The processing of beta-amyloid precursor protein (betaAPP) and its metabolites plays an important role in the pathogenesis of Alzheimer's disease (AD) and Down's syndrome. The authors have reported elsewhere that a targeted mutation resulting in low expression of a shortened betaAPP protein (betaAPP(delta/delta)) entails reduced learning abilities. Here the authors investigate whether these effects were caused by postnatal developmental actions of the altered protein. The authors examined 35 mice carrying the betaAPP(delta/delta) mutation for somatic growth and sensorimotor development during the first 4 postnatal weeks (pw) and compared them with 31 wildtype litter-mates. Thereafter, the same mice were tested at about 10 weeks of age for openfield behavior and for swimming navigation learning. Mutant mice showed both transient and long-lasting deficits in development. Body weight deficit started to emerge at postnatal day (pd) 12, peaked with a 15.1% deficit at pd 27 and lasted until pw 33-37. Significant transient deficits in mutant mice during sensorimotor development were observed in three time windows (pd 3-10, pd 11-19 and pd 20-27), long-lasting effects, manifest at pw 8-12 and pw 33-37, emerged at any of the three periods. In the adult mice, exploratory activity of betaAPP mutants in the openfield arena was severely reduced. In the Morris water maze task, mutant mice showed moderate escape performance deficits during the acquisition period but no impairment in spatial memory. The authors conclude that a defective betaAPP gene impairs postnatal somatic development, associated with transient as well as long-lasting neurobehavioral retardation and muscular weakness. Comparison with earlier data suggests that early postnatal handling may attenuate some of the non-cognitive performance deficits in the water maze. Further, the manifestation and time course of behavioral yet not neuropathological symptoms in betaAPP mutant mice resemble in some aspects those of the human Down's syndrome.