We have investigated the effects of short- and long-term pinealectomy on the density of melatonin receptors in both the suprachiasmatic nuclei (SCN) and pars tuberalis (PT) of the rat. Short-term pinealectomy (conducted 3-5 days before sacrifice) induced a significant increase in the density of melatonin receptors in both structures. This increase can be interpreted as an up-regulation of melatonin receptors following the absence of plasma melatonin. In contrast, 7 days after pinealectomy, the receptor density began to decrease, reaching a low point 1.5 months after pinealectomy. At this time, the decrease represents a 40-45% reduction in binding sites as compared with values measured 3-5 days after pinealectomy. This slow decrease could be related to a slowdown of melatonin receptor synthesis. These results suggest that melatonin has a stimulatory effect on its own receptor synthesis. However, at 1.5 months after pinealectomy a novel equilibrium between synthesis and hydrolysis seems to be reached. Melatonin does not appear to be indispensable for the synthesis of its receptors.