Ethnicity, cutaneous nevi and eye color are generally accepted risk factors for melanoma of the eye, although casecontrol studies have produced conflicting results. We sought to determine the constitutional risk factors for melanomas of the choroid, ciliary body, iris and conjunctiva in Australia. A population-based case-control study was conducted, with case ascertainment from a prospective national incidence survey and randomly selected community controls. Two hundred and ninety cases aged 18 -79 years and diagnosed between 1st January 1996 and 31st July 1998 were enrolled with 916 controls frequency matched by age, sex and State or Territory of residence. Risk of choroidal and ciliary body melanoma (n ؍ 246) was increased in people with grey (OR 2.9, 95% CI 1.5-5.5), hazel (OR 2.2, 95% CI 1.4 -3.7) and blue eyes (OR 1.7, 95% CI 1.0 -2.7) compared with brown eyes. Risk was also increased in those with 4 or more nevi on their back, those unable to tan, and those who squinted when outdoors as a child. Risk was reduced in people born other than in Australia and New Zealand (OR 0.7, 95% CI 0.5-1.0). Non-brown eye color was a risk factor for iris melanoma (n ؍ 25). No risk factors were identified for conjunctival melanoma (n ؍ 19). Eye color is the strongest constitutional predictor of choroidal and ciliary body melanoma, and may indicate a protective effect of melanin density at these sites. An independent association with cutaneous nevi suggests a role for other genetic factors.