Autoradiolysis of therapeutic doses of monoclonal antibodies can occur rapidly, limits their shelf life and makes onsite radiolabeling a near-necessity. We evaluated freezing of three different 131I-labeled murine monoclonal antibodies at -70 degrees C, immediately following radiolabeling, as a method of diminishing autoradiolysis, and of preserving immunoreactivity. Freezing greatly limits the ability of radiation-induced free radicals to diffuse in solution and thus produce radiolytic damage. By freezing at -70 degrees C autoradiolytic damage of immunoreactivity of three different 131I monoclonal antibodies could be largely eliminated, in contrast to the 80-90% losses in immunoreactivity seen with storage at 4 degrees C for a period of 1 to 12 days. Reduced in vitro deiodination rates are also seen for frozen antibodies. Limited studies with 125I-labeled antibodies indicate autoradiolysis does occur, though at a slower rate per mCi than for 131I, and that this process is also retarded by freezing. Freezing may be valuable while quality control procedures are performed following radiolabeling as well as if temporary storage or shipment of radioantibodies prior to patient dosing is undertaken. While the approach should be validated for each antibody studied, freezing of therapeutic doses of monoclonal antibodies appears to be a simple and effective approach to the problem of autoradiolysis.