Radioembolization is used in diagnostic imaging of the lungs and for radioembolization therapy of hepatic tumours. Presently, Tc-99m labelled macroaggregates or microspheres of human serum albumin (HAM) are used for this purpose. Poly lactic acid (PLA) is biodegradable, like HAM, and, unlike HAM, is not a blood product. The aim of the present study was to evaluate the uptake and biodegradation of PLA microspheres in lungs. PLA (MW=48 720 Da) microspheres of 1.0-100 mu m (mean = 39.5 mu m) in diameter were prepared by solvent evaporation from methylene chloride. They were labelled with Tc-99m by stannous chloride reduction at pH 3, with an efficiency of 98% and a stability of 96% at 24 h. For biodistribution studies, 15 mice were i.v. injected with 20 mu Ci Tc-99m-PLA microspheres in 0.1 ml and sacrified at 15 min, 1, 3, 6 and 24 h (three at each time point). All the organs were removed, weighed and counted against a standard prepared from 1/100 dilution of the injected radioactivity. Some mice were similarly injected and sacrified at 30 min, 15 and 30 days. The lungs were removed and frozen, and 10 mu m sections were obtained, stained with haemotoxylin and eosin and examined under a light microscope. Five rabbits were i.v. injected with 1 mCi of Tc-99m-PLA microspheres. Scintigrams were obtained at various intervals up to 24 h. In mice, the lung uptake was significant at 30 min-1 h post-injection. In rabbits, the lungs were the only organs visualized up to 24 h. Microscopic examination of tissue sections demonstrated slow biodegradation of PLA particles. In conclusion; (1) The high lung uptake obtained in mice and rabbits indicates the suitability of PLA microspheres for lung imaging, and (2) although the slow biodegradation rate might be a disadvantage in patients with lung disorders in diagnostic studies, it may be an advantage in therapeutic applications with radionuclides which have long physical half lives.