Streptococcus pneumoniae causes a significant amount of illness and death from pneumonia, bacteremia and meningitis among children < 2 years of age. No currently available effective vaccine exists to prevent pneumococcal disease in this age group. To identify modifiable risk factors we conducted a retrospective case-control study of 29 Alaska Native residents of Bethel, AK, < 2 years of age who had invasive pneumococcal illness from 1983 to 1992 and 85 controls matched for race, city of residence and date of birth. Data were collected through reviews of medical records and telephone interviews. In matched univariate analysis the following variables were associated with illness at P < or = 0.25 and were included in the multivariate model: at least one prior episode of pneumonia; at least one prior hospitalization; group child care center attendance; at least one tobacco smoker in the household; at least one tobacco chewer in the household; and lack of breast-feeding. Using a conditional multiple logistic regression analysis, we found that group child care center attendance (odds ratio, 98.6; 95% confidence interval, 5.1 to 1920.6) and the presence in the household of at least one person who chewed tobacco (odds ratio, 20.6; 95% confidence interval, 1.4 to 294.5) were independently associated with illness while breast-feeding was protective (odds ratio, 0.1; 95% confidence interval, 0.0 to 1.0). These data suggest that breast-feeding may prevent invasive pneumococcal disease and that strategies for decreasing risks should target children in group child care settings. Further studies are needed to evaluate the interaction of tobacco and pneumococcal illness.