Monoclonal antibodies are assuming increasing importance in experimental and clinical medicine. Generally, tissue biodistribution studies in animals precede human studies. To investigate a concern of ours that varying methods of sample handling in these studies could result in apparent alterations in tissue-binding levels, we compared two methods of tissue processing after the administration of labeled antibodies: one including only blotting away of blood, the other involving several washing steps. The unwashed, blotted specimens were found to have significantly more radioactivity per gram of tissue than the washed, ranging from 22% more in the spleen to 52% more in the lungs and left ventricle. Since in vivo imaging is dependent on the total mount of radioactivity in an organ, we believe the most meaningful determination of tissue radioactivity should be based on unwashed samples. Awareness of this problem is suggested to allow meaningful extrapolations from measured tisue localization data to imaging and therapy.