The involvement of serotonin (5-hydroxytryptamine; 5-HT) in immunoregulation has been well documented. Gut mucosa is a large reservoir of 5-HT most of which is attributed to gut endocrine cells. In this study, we examined the anatomical relationship among 5-HT immunoreactive cells and T and B lymphocytes in the gut mucosa of rhesus monkeys (Macaca mulatta). 5-HT, CD3 and CD20 immunoreactive cells were immunofluorescently labeled and visualized by confocal microscopy. 5-HT immunoreactive cells were primarily found within the epithelium of the intestine and were present at all levels of the gastrointestinal tract. Many 5-HT immunoreactive cells were in contact with, or very close proximity to CD3(+) and CD20(+) lymphocytes. These results provide morphological evidence to suggest interactions between 5-HT secreting enteroendocrine cells and lymphocytes in the gut mucosa. This further supports a possible role of 5-HT in mucosal immune responses.