Introduction 3. Melatonin receptors 3.1. MT1 and MT2 melatonin receptors 3.1. 1. Molecular structure 3.1. 2. Pharmacology 3.1. 2.1. Efficacy, potency and affinity 3.1. 2.2. Ligand selectivity 3.1. 2.3. Ligand specificity 3.1. 3. Signaling 3.1. 4. Regulation 3.2. MT3 melatonin receptors 3.3. The same ligand can change efficacy 3.3. 1. Efficacy of luzindole and 4P-PDOT at MT1 melatonin receptors 3.3. 2. Efficacy of luzindole and 4P-PDOT at MT2 melatonin receptors 4. Physiological responses mediated by activation of specific melatonin receptors (MT1, MT2, and MT3) 4.1. Melatonin receptors in the central nervous system 4.1. 1. The circadian timing system 4.1. 2. Melatonin regulation of neuronal firing rate and circadian timing 4.2. Regulation of the hypothalamic-hypophyseal-gonadal axis 4.3. Regulation of cardiovascular functions and temperature 4.4. Regulation of cell-mediated and humoral immune responses and inflammation 5. Summary and perspective