Cytogenetic investigations of posterior uveal melanomas have identified non-random changes of chromosomes 3, 6, and 8. Monosomy of chromosome 3 with additional copies of 8q occur principally in the subgroup of uveal melanomas arising from the ciliary body. To determine whether ciliary body and choroidal melanomas maintain submicroscopic differences in their genetic aetiology, studies of the loss of heterozygosity (LOH) of THRB (ERBA beta) on 3p were undertaken. DNA from the blood and tumours of 19 patients with uveal melanoma were analysed for LOH of two restriction fragment length polymorphisms (RFLP). Approximately 60% of the uveal melanomas demonstrated allelic loss of THRB. Although the majority of tumours with allelic loss originated wholly, or in part, from the ciliary body, choroidal melanomas also demonstrated allelic loss of THRB. These results suggest that deletions of chromosome 3 occur in the absence of visible cytogenetic changes and may imply that alterations of chromosome 3 are integral to the tumourigenesis of both sets of uveal melanomas.