In two experiments sex differences in changes in central noradrenergic, dopaminergic and serotonergic activity were measured immediately after a 30-min session of inescapable footshocks. In Experiment 1 concentrations of noradrenaline, dopamine, serotonin and their major metabolites were determined in the frontal cortex, hypothalamus, amygdala, striatum, mesencephalon and the medulla-pons area. Inescapable shock increased the activity of all 3 transmitter systems, as evidence by increased metabolite concentrations in specific brain areas. Shock-induced increments in metabolite levels were larger in females than in males, especially for the serotonergic system. In addition, shock presentation resulted in a decrement in the noradrenaline content in most areas studied. In the frontal cortex, noradrenaline was reduced by inescapable shock in males but not in females. In Experiment 2, sex-dependent neurochemical consequences of predictable versus unpredictable shocks were studied in the frontal cortex and the medulla-pons area. Similar to Experiment 1, both brain parts showed large shock-induced increments in the activity of the catecholaminergic systems. Differential effects of predictable and unpredictable shock were not found (frontal cortex) or were rather small (medulla-pons) and appeared sex-dependent for serotonin in this area. The sex differences in neurochemical change found in the first experiment were largely replicated in the second experiment. The relevance of the observed sex differences in central neurotransmitter reactivity for sex differences in behavior is discussed.