Specific 3H-kainate binding to membrane homogenates of rat cerebral cortex was compared in three paired groups: (i) acute methamphetamine (MAP) (4 mg/kg, ip) or saline; (ii) MAP or saline for 14 days followed by 7 days abstinence; and (iii) MAP or saline for 14 days, 7 days abstinence, and an acute test dose of MAP (4 mg/kg). Acute MAP administration did not produce any alteration in density or affinity of either high- or low-affinity kainate binding sites. Chronic MAP exposure lowered the density of high-affinity kainate binding sites (approximately 10% reduction). Acute readministration of MAP after chronic injections did not cause further changes. The decrease in density of high-affinity binding sites was seen only after repetitive MAP. This reduction was present equally in both anterior and posterior parts of the cerebral cortex. Such changes might share the mechanisms responsible for the susceptibility to MAP-induced behavioral supersensitivity and psychotic states.