In this study, we aimed to establish whether domestic use of wood fuel is associated with reduced birth weight, independent of key maternal, social, and economic confounding factors. We studied 1,717 women and newborn children in rural and urban communities in rural Guatemala. We identified subjects through home births reported by traditional birth attendants in six rural districts (n = 572) and all public hospital births in Quetzaltenango city during the study period (n = 1,145). All were seen within 72 hr of delivery, and data were collected on the type of household fuel used, fire type, and socioeconomic and other confounding factors. Smoking among women in the study community was negligible. Children born to mothers habitually cooking on open fires (n = 861) had the lowest mean birth weight of 2,819 g [95% confidence interval (CI), 2,790-2,848]; those using a chimney stove (n = 490) had an intermediate mean of 2,863 g (95% CI, 2,824-2,902); and those using the cleanest fuels (electricity or gas, n = 365) had the highest mean of 2,948 g (95% CI, 2,898-2,998) (p< 0.0001). The percentage of low birth weights (< 500 g) in these three groups was 19.9% (open fire), 16.8% (chimney stove), and 16.0% (electricity/gas), (trend (p = 0.08). Confounding factors were strongly associated with fuel type, but after adjustment wood users still had a birth weight 63 g lower (p = 0.05; 95% CI, 0.4-126). This is the first report of an association between biofuel use and reduced birth weight in a human population. Although there is potential for residual confounding despite adjustment, the better-documented evidence on passive smoking and a feasible mechanism through carbon monoxide exposure suggest this association may be real. Because two-thirds of households in developing countries still rely on biofuels and women of childbearing age perform most cooking tasks, the attributable risk arising from this association, if confirmed, could be substantial.