Lung clearance of51CR and125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC‐1 tumor cells with125I,111In,99mTc, or67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti‐LY49C/1) (ab’)2mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the111In labeled cells. Lung clearance increased after 15 min (lodging: 60–80&percent;) and (2 h retention: 3–7&percent;). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with111In,99mTc or67Ga are cleared similar to those labeled with51Cr or125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc,111In,67Ga) or by PET (68Ga). © 2003 American Institute of Physics