The activity of serotonin N-acetyltransferase (NATase) in the rat pineal gland exhibits a large (approximately 100-fold) circadian variation, with peak activity occurring in the dark part ofthe light/dark cycle. Surgical removal ofboth superior cervical ganglia abolishes this rhythm in enzyme activity. Unilateral ganglionectomy caused a 75% decrease in NATase activity during the dark period immediately following the operation; however, by the subsequent dark period (32 hr after operation) the rhythm in NATase activity had returned to normal. Similar results were found after the internal carotid nerve was cut, and data are presented indicating that this is the postganglionic trunk by which sympathetic neurons reach the pineal gland. Denervation of one superior cervical ganglion (unilateral "decentralization") also produced a 75% decrease in NATase activity during the dark period immediately following the operation; however, after decentralization, enzyme activity did not return to normal in subsequent cycles. It is hypothesized that this recovery is due to loss of norepinephrine uptake sites in the degenerating sympathetic nerve terminals. As a result of decreased norepinephrine uptake, the effectiveness of the norepinephrine released by surviving neurons may be enhanced. This hypothesis is supported by experiments in which pharmacological blockade of norepinephrine uptake in unilaterally decentralized animals increased NATase activity to control levels. We propose that neural systems which use transmitter uptake as the mechanism of transmitter inactivation have a built-in "reserve stimulatory capacity."Although a great deal of interest has been focused in recent years on the ability of the nervous system to recover after subtotal neural damage, there are only a few systems available in which functional recovery has been studied quantitatively on a cellular level. A useful system for such an investigation should have two characteristics: (i) permit the making of a lesion of a reproducible size in a specific part of the nervous system, and (ii) permit quantitative measurement ofthe degree offunctional recovery after the lesion is made. The innervation of the rat pineal gland offers such a model system.The pineal gland is a midline structure innervated by adrenergic sympathetic neurons whose cell bodies are located in the right and left superior cervical ganglia (SCGs) (1-4). In the rat these ganglia are the primary source ofneurons innervating this tissue (3)(4)(5). Ganglionic neurons are important in regulating a number of aspects of the biochemistry of the pineal parenchymal cells, particularly the synthesis of the. hormone melatonin. Pinealocytes synthesize melatonin from serotonin in two steps catalyzed by the enzymes serotonin N-acetyltransferase (arylamine N-acetyltransferase, EC 2.3.1.5) (NATase) and hydroxyindole O-methyltransferase (acetylserotonin methyltransferase, EC 2.1.1.4).The sympathetic neurons innervating the pineal gland appear to constitute the final pathway by which changes in environ...