Methods for labeling antibodies with 99mTc cannot be used without modification for radiorhenium despite the similar chemistries, in part because of a lower redox potential of rhenium and therefore a greater tendency to reoxidize. We have investigated conditions for directly labeling B72.3 IgG with 188Re via both mercaptoethanol and stannous ion antibody reduction. The reduced 188Re was stabilized for transchelation as the glucoheptonate complex and transchelated in the presence of excess stannous ion. End points were low "non-specific" binding (i.e. labeling in the absence of antibody reduction) and increased stability to cysteine challenge. By both methods, labeling efficiencies after about 15 minutes averaged 58.77% with as little as 4% non-specific binding. Specific activities of 15 muCi/microgram was achieved after 1.5 hours. By investigating labeling condition, it was possible to improve the stability of the label on stannous ion reduced antibody such that the in vitro and in vivo properties of 188Re were largely independent of labeling method. For example, losses of 188Re due to oxidation (16%) and to cysteine (7%) during 37 degrees C serum incubations for 24 hours were identical for both methods. Furthermore, after the administration to normal mice, whole body clearance and the accumulations of 188Re at 2.5 and 24 hours in blood and in most organs were also independent of labeling method. In conclusion, two different direct labeling methods provided a 188Re-labeled antibody with identical stabilities and with in vivo properties not greatly different from that seen for the same antibody radiolabeled directly with 99mTc.