OBJECTIVE: To determine the population-based incidence of disseminated bacille Calmette-Guérin (BCG) disease in HIV-infected infants (aged <or= 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants. METHODS: The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004-2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates. FINDINGS: The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361-1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587-2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377-1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567-1495) per 100 000. CONCLUSION: Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk-benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.