A total of 22 NZW rabbits with VX2 squamous cell carcinomas transplanted into the auricles were intra-arterially (i.a.) embolized with radioactive or inactive holmium-labelled poly(L-lactic acid) (HoPLA) microspheres with a mean diameter of 38-80 microm. The effects on tumour growth, the efficiency of i.a. infusion, the efficacy of retention of microspheres in the primary tumour and the excretion of free holmium-166 were analyzed. Complete tumour remissions were obtained in 79% and 86% following embolization with radioactive and inactive microspheres, respectively. Over 95% of the microspheres were retained in the tumour and the leaching of holmium-166 in urine and faeces was less than 0.1% in 2 days. The injection efficiency was not optimal, as 40% of the microspheres were retained in the cannulation system. Arterio-arteriolar connections should be detected and closed prior to embolization to prevent stray emboli from entering the brain. It is concluded that 166HoPLA microspheres are promising candidates for further studies on radio-embolization of unresectable head-and-neck cancer.