The mammalian pineal organ transduces light-dependent neural inputs into a hormonal output. This photoneuroendocrine transduction results in a largely elevated concentration of the pineal hormone melatonin at night. The rhythm in melatonin production and secretion depends on activation and inactivation of transcriptional, translational, and posttranslational mechanisms fundamentally linked to two second messenger systems, the cAMP- and the Ca(2+)-signal transduction pathways. Here we review molecular biological, immunocytochemical, and single-cell imaging studies, which demonstrate a time- and substance-specific activation of these signaling pathways in rat pinealocytes. The data provide a framework for understanding the complex interactions between second messengers (cAMP, Ca2+), transcription factors (CREB, ICER), and their role in regulation of melatonin synthesis. The data have proven the rat pinealocyte to be an interesting model to study transmembrane signaling pathways which may be common to both neuroendocrine and neuronal cells.