S-100 protein has been detected in epidermal Langerhans cells, interdigitating reticulum cells, and large mononuclear cells of cutaneous T-cell lymphomas. Experimental data imply these cells are involved in the presentation of antigens and/or maturation of T-lymphocytes. The authors studied the morphology and distribution of S-100 protein antigen-containing cells in cutaneous sarcoidosis and metal-induced granulomas, both immunogenic and foreign-body types, with light and electron microscopic immunoperoxidase technics. Immunological reaction was seen in Langerhans cells, peripheral nerves, and granulomatous lesion dendritic cells. The latter showed a large, irregular nucleus and branching cytoplasm. They intermingled with other mononuclear cells in the granulomas but not with organized epithelioid cells. Morphometric quantification of dendritic cells in the three types of granulomas revealed statistically significant differences (P less than 0.005) and electron microscopy demonstrated their typical cytoplasmic appearance, without Birbeck granules. The increased number of dendritic cells in immunogenic granulomas, and their shared antigenic components with Langerhans cells suggest they act as accessory cells in eliciting the granulomatous response.