This study characterizes regional regulation of adenylate cyclase by galanin, neuropeptide Y (NPY), secretin and vasoactive intestinal peptide (VIP) in rat brain frontal cortex, hypothalamus and hippocampus. In our experimental system, galanin caused small detectable activation (10-20%) of basal adenylate cyclase activity in frontal cortex and hippocampus but had no effect on basal adenylate cyclase activity in hypothalamus. Galanin inhibited forskolin-stimulated adenylate cyclase in all three brain regions-hypothalamus, hippocampus and frontal cortex by 54.5%, 44.3% and 25.7%, respectively. NPY reduced basal and forskolin-stimulated enzyme activities by 35% only in frontal cortex, but not in the other two brain areas. Secretin had no effect in frontal cortex but caused similar adenylate cyclase activation in hypothalamus and hippocampus. VIP had a stimulatory effect of 32.8% and 32.4% in frontal cortex and hippocampus, respectively. The results indicate regional differences in adenylate cyclase modulation by the four peptides and reveal interesting relations in comparison with peptide and receptor densities in the three investigated brain regions.