Eyes of 25 patients among a series of 100 consecutive patients who underwent iodine 125 brachytherapy for extremely large uveal melanomas measuring more than 7-8 mm in height had to be enucleated after an average interval of 1.4 years. The dose delivered to the tumor apex was 120-150 Gy. Indications for enucleation were most frequently radiation-induced alterations in the anterior segment with loss of fundus visibility. Eight cases showed insufficient tumor regression, and two cases were suspicious for growth. Microscopically complete tumor necrosis was found in ten eyes. Six cases were classified as "uncertain tumor regression." Apparently "viable" tumor cells were seen in nine eyes. This group of eyes showed a significantly shorter interval between therapy and enucleation. One specimen showed extraocular tumor extension. Brachytherapy with iodine 125 may result in complete tumor necrosis, even in large uveal melanomas. The morphologic extent of tumor necrosis seems to be positively correlated with the interval after therapy.