Autologous T lymphocytes form broad, unspecialized, noninvaginating contacts with Reed-Sternberg cells in vitro. These differ from contacts between cytotoxic lymphocytes and their targets and from the uropodal type of lymphocyte adherence described in many antigen- (or mitogen-) dependent systems but show some resemblance to antigen-independent lymphocyte/macrophage contacts. Adherence is not confined to a specific T-cell subset; most adherent cells are negative for ANAE, Fc gamma, and Fc mu receptors. A minority have Fc mu or Fc gamma receptors or show ANAE staining. Adherence is dependent on divalent cations and intact surface proteins but is independent of temperature, cell metabolism, and intact microtubules and does not appear to be mediated by Fc gamma receptors or IgG. These characteristics distinguish it from immune T-cell/target-cell binding and from antigen-independent T-cell/macrophage or T-cell/B-lymphoblast binding. Contrary to previous suggestions, this interaction is not related to a cytotoxic attack. The lack of similarities with other lymphocyte adherence systems leads the authors to suggest that a unique receptor system is involved.