The presence of the heat shock protein (hsp-70) has been detected in exocytosed vesicles (which are named exosomes) from mammalian and avian immature red cells (i.e. reticulocytes) as well as from a differentiating avian erythroleukaemic cell line. The close, but non-covalent, association of hsp-70 with the transferrin receptor (TFR) in exosomes is demonstrated by: (1) the ability to cross-link hsp-70 to TFR; (2) the co-immunoprecipitation of hsp-70 and TFR with an antibody against TFR, and the co-immunoprecipitation of TFR and hsp-70 with antibody against hsp-70; and (3) the retention of TFR by hsp-70 bound to ATP-agarose and the simultaneous elution of both proteins by excess ATP. Semi-quantitative analysis of the relative efficiency of cross-linking of these proteins in exosomes versus plasma membranes shows that TFR in exosomes is preferentially bound to hsp-70. From an analysis of the relative amounts of hsp-70 and TFR regenerated from the cross-linked complex, the ratio of TFR monomer bound to hsp-70 is approximately 1.5 to 1. Given the presence of hsp-70 in exosomes from several species and its close association with TFR (the major protein lost during reticulocyte maturation) it is proposed that hsp-70 plays a role in exosome formation and/or release in immature red cells.