T-cell clones and cell lines which apparently respond to autologous (syngeneic) erythrocytes have been generated from the spleens of normal mice. The response showed considerable cross-reactivity with red blood cells (RBC) from other species, including chicken, and was 'heteroclitic' in that reactivity against some species of RBC, notably rat and monkey, was greater than to mouse. The clones were Thy-1+ L3T4+ Lyt-2- and recognized antigen in association with I-Ak or I-Ek. At least three specificities were identified on the basis of reactivity to crude lysates of mouse and rat RBC. One of the putative clones, M0.5/1/D2, showed a change in reactivity during culture, proliferating strongly against antigen-presenting cells (APC) without added erythrocytes. Analysis of the clones and lines using an I-Ak I-Ek expressing hybridoma, HB-98, has indicated that only one, M5/1/F5, was likely to be erythrocyte-specific; the remainder were responding to antigens present in foetal calf serum (FCS). The data demonstrate that apparent erythrocyte specificity can be a result of serum components being presented to T lymphocytes via red blood cells.