The purpose of this investigation was to determine the targeting potential of the murine monoclonal antibody (MAb) RNL-1 for human small-cell lung cancer (SCLC) in a nude mouse model. RNL-1 is preferentially reactive with SCLC and lung carcinoids, and was classified as a cluster-1 MAb as defined by the International Workshop on Small-Cell Lung-Cancer Antigens. From the intercellular location of the target antigen and its reactivity with 3T3 cells transfected with nucleic acid sequences encoding for the neural cell adhesion molecule (NCAM), it was concluded that RNL-1 is directed against NCAM. RNL-1 was radiolabelled with either 125iodine or 111indium and injected into nude mice bearing NC1-H82 SCLC xenografts. The biodistribution of the radiolabels was determined up to 120 hr post injection. Maximum tumour accretion for 111In-RNL-1 was 11.8%ID/g and 6.5%ID/g for 125I-RNL-1. The accumulation of 111In-RNL-1 could be visualized clearly by gamma scintigraphy without background subtraction techniques. Autoradiographs of whole-body sections from animals injected with 125I-RNL-1 showed that activity in the SCLC xenografts was mainly peripheral, suggesting that tumour uptake is dependent on the vascularization of the tumour tissue.