Papillary carcinomas (PCs) of thyroid are among the most common but least aggressive human malignancies. The factors explaining the indolence of these tumors are unknown but host-tumor immune interactions may play a role. This study was designed to determine if there is morphologic evidence of these. Frozen tissues collected from 21 PCs, 4 follicular adenomas (FAs), 4 follicular carcinomas (FCs), and 11 nodular hyperplasias (NHs) were stained immunohistochemically for HlLA-D antigens, lymphocyte, and macrophage markers; results were graded numerically. Paraffin-embedded tumors (35 PCs, 10 FAs, and 10 FCs) were stained for 5-100 protein to detect Langerhans' cells (LCs). Diffuse staining for HLA-D antigens and heavy mononuclear infiltrates were found more commonly in PCs compared to follicular neoplasms (FNs) or NHs. No consistent relationship was found between lymphocyte/macrophage infiltrates and expression of HLA-D antigens. The largest number of LCs was in PCs (median 11.8 cells/standard microscopic field [c/smf]), fewer cells were found in FA (3.7 c/smf), and the least in FC (0.05 c/smf). Features of host-tumor interaction including HLA-D expression and infiltrates with lymphocyte macrophages and LC are more strongly expressed in PC than other tumors. This may play a role in explaining their biological behavior.