In clinical populations, sex differences in disease prevalence, symptoms and outcome have been established. Despite this, female rats are frequently omitted from preclinical research; growing preclinical evidence, however, illustrates meaningful sex differences in behavioural, neurochemical and neuroanatomical endpoints. This review outlines the effects of sex on tests of depression- and anxiety-like symptoms, learning and memory, and responses to stress in rats. In addition, sexual dimorphisms in monoamine neurotransmitter and neurotrophic factor levels, neurogenesis and plasticity, and responsiveness to drugs of abuse are reviewed. Female rats display greater baseline activity levels compared to males, test-specific sex differences also exist in learning and memory protocols as females respond more actively in conditioning paradigms and are somewhat impaired in tests of spatial memory compared to males. Differential baseline and stress-induced hypothalamic-pituitary-adrenal axis responses between male and female rats depend on the nature of the stressor. Females are more responsive to the effects of psychomotor stimulant drugs; sexual dimorphisms in response to psychotropic drugs are likely mediated by neurochemical differences between male and female rats. Differences exist in neurotransmitter activity, transporter and receptor expression between the sexes. Studies of ovariectomised and intact female rats demonstrate a potent impact of elevated estrogen during the estrous cycle on behaviour, neurochemistry, dendritic growth and drug response. Sex differences in baseline behaviours and the methodological procedures employed can influence behavioural pharmacology result interpretation. In addition, the inclusion of both male and female rats in studies investigating neurochemistry and neuromorphology may enhance the validity of drug or rehabilitative treatments. (C) 2011 Elsevier B.V. All rights reserved.