The metabolism of histamine and transport of its precursor histidine were investigated in rat brain synaptosomes which underwent the ADP-Fe/ascorbate-induced peroxidation. Peroxidation impaired histidine uptake by 40%, and veratridine induced release of it by 25% of maximal uptake. Simultaneously, marked decrease of synaptosomal histamine (HA) content, to about 30% of control value, was found (p less than 0.01). Activity of the two histamine-metabolizing enzymes, histidine decarboxylase (HD) and histamine N-methyl-transferase (HMT), were drastically lowered, by 40% (p less than 0.02) and 60% of control (p less than 0.05), respectively. Pretreatment of rats with glucocorticoid analog, dexamethasone (DMX), 1 mg/kg of body weight, given twice, 20 and 2 h before decapitation, did not influence significantly the effects invoked by peroxidation on HA levels and the activity of HD and HMT, but impaired histidine transport. These results indicate that iron-dependent peroxidation decreases both neuronal pool of histamine and its turnover, which may affect the function of central nervous system. Short pretreatment with dexamethasone does not seem to influence this effect.