The dendritic and the interdigitating (IRC) reticulum cells had different topographical distribution in the human lymphoid tissue and some peculiar cytochemical and immunohistochemical features. These included the detection of S-100 protein by PAP (peroxidase anti-peroixdase) method only in IRC located in the thymus-dependent areas. In 15 reactive lymphoid tissue specimens (11 lymph nodes, 3 tonsils and 1 adenoid) the presence of S-100 protein was tested by ABC (avidin-biotin complex) immunoperoxidase method. IRC were constantly positive. Other positive cells were located within the follicular germinal centers; these immunostained cells appeared as a striking network composed of dendritic-shaped processes displaying a finely granular positivity for S-100 protein. By using this very sensitive technique, S-100 protein can also be detected in intrafollicular cells of dendritic morphology.