The aim of this study was to see whether neonatal handling can reverse the behavioral deficits induced in rats by unpredictable prenatal stress. Rats (24) were exposed to random noise and light stress (RS) on a random basis throughout pregnancy. Half the litters of RS and control (C) dams were subjected to neonatal handling (NH), 3' daily for 21 days. Behavioral measures, open field in both sexes and plus maze test in females only were conducted at 1.5-2 months, and spatial lateralization by amphetamine-induced rotation, in females at 3 months. RS caused significant increases in emotionality and timidity (higher incidence of defecation and less time in open arms of plus maze), and a change in directional bias towards the left. NH completely reversed all these behavioral abnormalities in RS rats but had little effect in C. It is concluded that NH can influence postnatal development of brain organisation in the opposite direction to that induced by prenatal stress.