Most patients with ovarian cancer have disease in the peritoneal cavity. Treatment of this region is inadequate because recurrences are frequent. Increased radiation doses to tumor and, hence, greater tumor control may be possible with intraperitoneal (i.p.) administration of radiolabeled human monoclonal immunoglobulin M (IgM), which is reactive with tumor-associated antigens. Biodistribution studies were performed in nude mice bearing i.p. nodules of human ovarian cancer after administration of human monoclonal IgMlambda (AC6C3-2B12), labeled with 111In or 90Y. Irrelevant 111In-labeled human IgMlambda (CH-1B9) and 90Y-aggregate served as specificity controls. Intravenous administration of 111In-labeled AC6C3-2B12 produced low tumor and high liver and spleen uptake. Intraperitoneal administration of AC6C3-2B12 labeled with 111In or 90Y resulted in rapid, high tumor uptake (>45% of injected dose per gram of tumor at 3 hr) that was at least three-fold higher than any normal organ. Biodistribution results were similar for 111In- and 90Y-labeled IgM. Tumor uptake of 111In-labeled AC6C3-2B12 was two-fold greater than that of 111In-labeled CH-1B9. Normal organ uptakes were similar for tumor-reactive and irrelevant IgM. Radioimmunoconjugates were retained in the peritoneal cavity for a prolonged period of time. Yttrium-90 aggregate demonstrated high tumor and bone uptake. Higher tumor uptake was observed after i.p. administration of tumor-reactive IgM than after irrelevant IgM. The in vivo behavior of tumor-reactive IgM was similar when it was radiolabeled with either 111In or 90Y. Therefore, 111In-based imaging studies can be used to predict the biodistribution of subsequently administered 90Y-labeled IgM. Further development of radiolabeled AC6C3-2B12 as a diagnostic and therapeutic agent for patients with advanced ovarian carcinoma is warranted.