BACKGROUND: Host-related and environment-related factors have been shown to play a role in the development of tuberculosis (TB), but few studies were carried out to identify their respective roles in resource-poor countries. METHODS: A multicentre case-control study was conducted in Guinée, Guinea Bissau, and The Gambia, from January 1999 to March 2001. Cases were newly detected smear positive TB patients. Two controls were recruited for each case, one within the household of the case, and one in the community. RESULTS: Regarding host-related factors, univariate analysis by conditional logistic regression of 687 matched pairs of cases and household controls showed that TB was associated with male sex, family history of TB, absence of a BCG scar, smoking, alcohol, anaemia, HIV infection, and history and treatment of worm infection. In a multivariable model based on 601 matched pairs, male sex, family history of TB, smoking, and HIV infection were independent risk factors of TB. The investigation of environmental factors based on the comparison of 816 cases/community control pairs showed that the risk of TB was associated with single marital status, family history of TB, adult crowding, and renting the house. In a final model assessing the combined effect of host and environmental factors, TB was associated with male sex, HIV infection, smoking (with a dose-effect relationship), history of asthma, family history of TB, marital status, adult crowding, and renting the house. CONCLUSION: TB is a multifactorial disorder, in which environment interacts with host-related factors. This study provided useful information for the assessment of host and environmental factors of TB for the improvement of TB control activities in developing countries.