The concentration of delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) in rat brain regions was determined by radioimmunoassay following treatment with various psychoactive drugs or adrenalectomy. The antidepressant drugs imipramine and zimeldine, given orally twice daily for three weeks, reduced the concentrations of DSIP-LI in the hypothalamus, frontal cortex and cerebellum. The effects of zimeldine were similar but somewhat less pronounced than those of imipramine. The neuroleptic drug haloperidol, given i.p. once daily for two weeks, increased the concentration of DSIP-LI in the hypothalamus, but not in the frontal cortex. A single dose of haloperidol did not affect the concentration of DSIP-LI in either region. Like haloperidol, pentobarbital elevated the concentration of DSIP-LI in the hypothalamus; however, this effect of the barbiturate was seen after single but not after repeated administration. Cortical concentrations of DSIP-LI were unaffected following both single and repeated pentobarbital administration. Finally, adrenalectomy increased the concentration of DSIP-LI in the hypothalamus, but not in the other brain regions. In conclusion, the DSIP concentration in rat brain regions may be altered by a variety of interventions. The most profound and general alterations were observed following administration of antidepressant drugs.