During the past 8 years numerous patients have been injected with radiolabeled monoclonal antibodies for both the diagnosis and treatment of cancer. In general the results, while somewhat promising, have failed to fulfill initial expectations. It is now clear that there are many physiologic barriers that antibodies face in their trek toward their tumor-binding site. Use of terms such as antibody-guided delivery or antibody-guided targeting do not take into account the fact that the antibodies are subject to the same physiologic rules as drugs and hormones. Antibodies are no more 'guided' than any drug or hormone. They reach their binding site via the same delivery mechanisms and accumulate in proportion to their 'receptor's' (antigen's) density. Our knowledge and understanding of the physiologic barriers to the uptake of tumor-associated monoclonal antibodies is limited. To date very few studies have been reported that shed light on this problem. For radiolabeled monoclonal antibodies to fulfill their promise, a greater understanding of these physiologic barriers is needed in order to devise ways in which they may be overcome.