Our work investigates changes that take place in the brain when organisms attempt to deal with stress. Human data suggest that differences in cerebral asymmetry play a role in determining the nature of the stress response. Results of our studies indicate that brain asymmetry also determines variation in stress-related behavior in rodents. Behavioral differences among rats are accompanied by distinct neurochemical and morphologic differences in brain regions controling particular aspects of the stress response. Animal models of human behavioral function and psychopathology have been used in our laboratory to study the way chemical and morphological asymmetries may affect behavioral differences. Turning behavior has been used in our laboratory as an index of asymmetric organization of the rodent brain. We have shown that rats exhibiting directional differences in turning preference (left and right turning rats) differ in various aftereffects of stress such as depression. Brain asymmetry also determines certain aspects of the response to antidepressant drugs. We have more recently extended these observations to show that differences brain asymmetry and in turning preference predict differences in amounts of spontaneous voluntary alcohol ingestion. Differences in stress-related behavior and alcohol consumption appear to be determined in part by variation in the organization of dopamine neurons projecting to the medial prefrontal cortex, an area that is important in governing thought and emotion. Related findings have also shown that a predilection toward cocaine and opiate abuse is also associated with a similar asymmetry of medial prefrontal cortex dopamine neurons. Results from behavioral assessment, chemical brain lesion and analytical neurochemistry studies are revealing how differences in brain asymmetry are linked to individual differences in behavior. They are providing insight as to why people differ in stress reactivity and in susceptibility to stress-related pathology such as depression and drug and ethanol abuse.