The normal or “resting” level of thymic histidine decarboxylase (HDC) enzyme activity in rats has been found to be quite high in comparison with the normal or “resting” levels observed in prior studies of other lymphoid organs. The resting level of activity is affected by age. It is higher in young rats and lower in old rats. The effect of organ allografting (heart and kidney) and of nonallografting surgical stress (renal isografting and simple laparotomy) on thymic HDC activity in the initial 10 days following operation was studied in 113 inbred Lewis rats. Both organ allografting and simple surgical stress produced a marked early (days 1 and 2) depression in thymic HDC activity. A significant later increase in thymic HDC activity above normal levels occurred after cardiac allografting. A mild decrease in thymic weights occurred. Lower thymic weights often were associated with high levels of thymic HDC activity. It is suggested that thymic HDC activity may play an important role in normal thymus function and in the thymic response to immunologic and nonimmunologic surgical stress. These changes may be involved in the release and recruitment of lymphoid cells to and from lymphoid organs and also may be related to changes in the metabolism of other vasoactive substances in thymic and other lymphoid tissues, to vasoactive substance receptors on lymphocytes, and to levels of lymphoid cellular cyclic adenosine monophosphate (AMP) activity.