BACKGROUND: There have been suggestions that when two or three unexpected unexplained infant deaths occur within a family they are more likely to be unnatural than natural. We aimed to estimate the probability that a second infant death is natural versus unnatural. METHODS: The Care of Next Infant programme (CONI) supports parents who have previously had an unexpected and apparently unexplained infant death and is currently available in over 90% of health districts in England, Wales, and Northern Ireland. We studied all deaths in 6373 infants who had completed the CONI programme by December, 1999. After a CONI death, we made detailed enquiries into the previous death and the CONI death, including a family interview, a review of autopsies, and case discussion. FINDINGS: 57 (8.9 per 1000) CONI infants died. Nine deaths were inevitable, and 48 were unexpected. 44 families lost one child, and two families lost two children. Of the 46 first CONI deaths, 40 were natural; the other six were probable homicides, five committed by one or both parents (two criminally convicted). The ratio of 40 natural to six unnatural deaths is 6.7 (95% CI 2.8-19.4). Enquiries identified 18 families with two SIDS(sudden infant death syndrome) deaths and two families with probable covert double homicides (ratio 9.0 [2.2 to 80.0]). There were no convictions in 13 incomplete cases. Families with three deaths are reported. INTERPRETATION: Repeat unexpected infant deaths are most probably natural.