Studies were conducted in rats to investigate whether chronic haloperidol treatment, electroshock treatment (EST), or a combination of both affects the high-affinity binding of 3H-imipramine to cerebral membranes. Chronic haloperidol (2 mg/kg SC daily for 28 days) resulted in a significant decrease in the density of binding sites in animals killed 1 h after the last treatment, but binding was markedly enhanced after a "washout" period of 5 days. In animals subjected to EST (20-30 mA, 1.5 s, 60 Hz; three times a week for 4 weeks) and killed 1 h after the last treatment, there were no apparent changes, but when animals were allowed a recovery period of 5 days there appeared to be a slight increase in binding. The marked increase in binding seen after haloperidol withdrawal was no longer apparent in animals treated with both haloperidol and EST, indicating that EST acts to attenuate the increase in binding seen after withdrawal of chronic haloperidol. It is suggested that chronic haloperidol may influence presynaptic recognition sites that regulate serotonin uptake and that EST may interact with haloperidol to "stabilize" these presynaptic sites.