The radioiodinated tetrapeptide delta-opioid antagonist [(125)I]ITIPP(psi) [H-Tyr(3'I)-Ticpsi[CH2NH]Phe-Phe-OH] (Ki(delta) = 2.08 nM; Ki(micro)/Ki(delta) = 1280) has been synthesized and evaluated as a potential lung tumour imaging agent. [(125)I]ITIPP(psi) was obtained, via electrophilic iodination, in 46% yield (>44,000 MBq/micromol) from the parent TIPP(psi). The biodistribution of [(125)I]ITIPP(psi) in nu/nu mice bearing SCLC-SW210.5 xenographs revealed good uptake and prolonged retention of radioactivity in organs known to possess delta-opioid receptors. Metabolite analysis showed that [(125)I]ITIPP(psi) was largely unmetabolized at 25 min PI and blocking studies showed significant reduction of uptake of the tracer in the brain, liver, intestine and tumor indicating that the iodinated tetrapeptide binds to delta opioid receptors in vivo.