BACKGROUND: Examination of families represents an important priority in health research. In this paper we report on individual and family-level factors associated with enrollment in a cancer prevention research project. We approached families affected by melanoma for possible participation in a randomized controlled trial of a web-based communication and support intervention. METHODS: We recruited three family members per family for assessment – the melanoma case, a first-degree relative (FDR), and a relative who is a parent of a child age 18 or younger. Recruitment involved three steps: requesting the physician’s consent to approach the melanoma case, approaching the case to request their participation and family contact information, and they approaching the FDRs and parents. RESULTS: Of the 1380 families approached, 313 were enrolled, 263 were excluded because we could not find or contact a family member (FDR or parent), 331 did not have eligible family members, and 473 refused. The most frequently noted reason for refusal was being too busy or having no time. The primary predictors of participation for cases (OR=1.6; CI=1.01-2.51) and FDRs (OR=2.15; CI=1.11-4.13) included higher educational attainment. FDRs were more likely to enroll if they were female (OR=1.77; CI=1.1-.85) and parents were more likely to enroll if the case had been diagnosed more recently (OR=3.3; CI=1.9-5.93), if the parent was partnered (OR=4.37; CI=1.86-10.26), and if the parent lived in the same city as the case (OR=2.88; CI=1.08-7.68). CONCLUSIONS: The results can provide information on potential directions for future family recruitment.