Due to contrary results concerning the interaction of cholecystokinin and dopamine (CCK/DA) circadian variations in CCK/DA concentration were investigated in forebrain nuclei of rats (Nc. accumbens, striatum) in order to assess the influence of time of day on neurotransmission. CCK was determined by a radioimmunoassay, DA was measured by electrochemical detection after HPLC separation. A distinct circadian rhythm, superimposed by harmonics (12 h, 6 h) was found in the content of both DA and CCK. A trough was shown for CCK during the light phase and a crest during the late afternoon and the dark phase, respectively. For DA the opposite was found. Caused by a phase-shift of about 3-4 h, the CCK/DA rhythms are negatively correlated. The differences are significant at 11.00 h, 13.00 h, 21.00 h, and 03.00 h. The results indicate that circadian processes are involved in neuronal transmission of CCK and DA.