Few studies have investigated the risk factors for tuberculosis (TB) infection in highly endemic countries. We conducted a household study in The Gambia, in which a tuberculin skin test (TST) was performed in members of the households of 315 smear-positive pulmonary TB cases and 305 community control subjects. The risk of being TST positive (10 mm or more) was higher in contacts of cases than in contacts of control subjects. It increased with age, male sex, and duration of stay in the household but was not associated with the presence of a bacille de Calmette-Guérin scar. Within the households of the TB cases, the risk of TST positivity was higher in males and was increased with age, social proximity to the case, and the radiologic extent of the disease in the case's chest X-ray. Adjusting on these, the risk of TST positivity was higher in first-degree relatives compared with more distant relatives and nongenetically related household members, but the effect was not statistically significant. In highly endemic areas, the risk of TB infection in contacts of TB infectious cases is associated with age, sex, intensity of exposure to the case, and severity of disease in the case, but it is possible that genetic factors contribute to the susceptibility to Mycobacterium tuberculosis infection.