A series of 1,438 parents and 2,663 other relatives of retinoblastoma patients have been followed up to ascertain the incidence among them of non-ocular cancer. Among 117 of these relatives who were known carriers of the mutation of the retinoblastoma gene 23 cases of non-ocular cancer developed during the follow-up period of the study. This compares with an expected number of 2.3, a relative risk of 9.9. A total of 25 deaths among these carriers included 21 from non-ocular cancer; the expected number was 1.8, a relative risk of 11.6. Relatives who are carriers are about 15 times more likely to die from lung cancer than the general population. Previous findings of an association of melanoma and bladder cancer with retinoblastoma are borne out in this study. The incidence of non-ocular cancer among relatives of hereditary cases who are not definitely known to be carriers shows an excess risk of 1.6: it is concluded that a proportion of these relatives are in fact carriers of the mutated retinoblastoma gene. For relatives who are not gene carriers there appears to be no excess risk of developing cancer. Carriers relatives who are not themselves affected with retinoblastoma may be inherently less liable than affected carriers to the further genetic changes which lead to the development of both retinoblastoma and subsequent non-ocular cancer.