Intraperitoneal tumors from a human cancer cell line (LoVo) were established in nude mice by i.p. inoculation of a single cell suspension. Two preparations of the same monoclonal antibody, radiolabeled with 125I and 131I were injected i.p. and i.v. into the same animals. Localization was assessed by dissection and counting the activity in tumors and normal tissues. Tumor/tissue ratios 1 h after i.p. injection of antibody were approximately 50 times higher than after i.v. administration. This i.p./i.v. advantage fell to around 4 by 8 h and was just greater than 1 by 24 h. This effect was observed with both specific and nonspecific antibody, indicating that it is due to the route of administration. However, the absolute amounts of antibody bound to tumors depended on the specificity of the antibody. Twenty % of the injected dose of specific antibody was bound per gram to tumor 1 to 2 h after i.p. injection, falling to 10%/g by 24 h and remaining at this level up to 5 days after antibody administration. In contrast, less than 10%/g of nonspecific antibody was detected in tumors after 1 h; this fell rapidly to normal organ levels of less than 5%/g by 8 h. This study demonstrates a major advantage when administering radiolabeled monoclonal antibodies i.p. for targeting intraperitoneal tumors.