Experimental results suggested a modulation or 'programming' interaction of delta sleep-inducing peptide (DSIP) with endogenous opioid-peptidergic systems and exogenous intracerebrally or systemically administered morphine and amphetamine. The induction of cerebral MAO-A activity, a pronounced influence on the circadian rhythms of locomotion and intracerebral neurotransmitter as well as plasma protein and cortisol concentrations has been reported. DSIP was also shown to counteract experimentally induced stress situations in animals. An improvement of the psychomotor performance and the concentration capacity in humans beside sleep normalization and pronounced effects on withdrawal symptoms including pain states in alcoholics and opiate addicts was discovered. This encouraged a pilot study for a possible action of the peptide in humans suffering from chronic pronounced pain episodes. We investigated the therapeutic effect in 7 patients with migraine episodes and vasomotor headaches, chronic tinnitus and psychogenic pain attacks. The anamnestic (baseline) values were statistically compared with the katamnestic control period. DSIP lowered significantly the pain levels of 6 out of 7 patients after intravenous administration on 5 consecutive days followed by 5 injections every 48-72 h. Remarkably, a simultaneous significant reduction of the concomitantly occurring depressive states was observed.