In rodents and humans stressful events in early life e.g. maternal deprivation, can increase sensitivity to stress in later life. Humans may become more susceptible to mood disorders, e.g. depression. In livestock species, such as pigs, early weaning is a form of maternal deprivation. We investigated behavioural consequences in 99 female pigs weaned at three different ages (12, 21 and 42 days; d12, d21, d42). Pigs were habituated to an open field arena over 6 days before being given 5-min open-field tests over three subsequent days (days 77-79). Early-weaned pigs (d12) showed behavioural inhibition (reduced vocalisations and lower activity) compared with later-weaned pigs, although in all groups these measures declined over the three tests, so this treatment difference might reflect more rapid habituation to the test in d12 pigs. Long-term effects on mood-related 5-HT receptor subtypes were measured in the brain at 90 days in a random sample of the d12 (n=8) and d42 pigs (n=8), using (3)H-ligand-binding and autoradiography and in situ hybridisation histochemistry. There were no differences between weaning ages in binding of (3)H-8-OH-DPAT (5-HT(1A) receptor agonist) or of (3)H-ketanserin (5-HT(2A) receptor antagonist) to any brain region studied. In d12 pigs, 5-HT(1A) receptor mRNA expression per unit area was 29%, 63%, 52% and 64% lower than in d42 pigs in the parvocellular PVN, amygdala and hippocampal dentate gyrus and pyramidal cell layer, respectively. The ratio of expression per cell to expressing cells per unit area was also lower, by 31%, in the pars horizontalis of the PVN in d12 pigs. Conversely, 5-HT(2A) receptor mRNA was expressed at a 25% and 28% higher density per unit area in the amygdala and pyramidal cell layer of the hippocampus, respectively, in these d12 pigs. In individual pigs, across brain regions, 5-HT(1A) receptor mRNA data were 70-79% correlated with binding data but no correlation was found for 5-HT(2A) data, suggesting different regulatory mechanisms. The behavioural and neurobiological responses to early weaning might represent either dysfunction or adaptation. Further investigation is required.