Transgenic hypertensive TGR(mREN2)27 (TGR) rats, carrying an additional mouse renin gene, have been found to show inverse circadian blood pressure profiles compared to normotensive Sprague-Dawley rats. In order to evaluate the contributions of the suprachiasmatic nucleus (SCN) and the neurohormone melatonin to cardiovascular circadian regulation in TGR(mREN2)27 rats and Sprague-Dawley (SPRD) controls, we investigated the effects of melatonin agonist and antagonist treatment in SCN-lesioned and nonlesioned rats, which were kept under conditions of alternating light and darkness (LD). After destruction of the SCN, circadian rhythmicity in blood pressure, heart rate (HR), and motor activity (MA) was almost abolished in rats of both strains. One week of treatment with a synthetic melatonin agonist S-21634 was not able to restore circadian variation in the parameters monitored. In nonlesioned TGR(mREN2)27 rats and Sprague-Dawley control rats, the melatonin antagonist S-22365 had no suppressive effect on LD-synchronized circadian rhythmicity, indicating that LD itself may have a stronger influence on the SCN than endogenous melatonin.