The U.S. infant mortality rate (IMR) increased from 6.8 infant deaths per 1,000 live births in 2001 to 7.0 in 2002, the first increase in more than 40 years. From 2001 to 2002, IMR increased for very low birthweight infants as well as for preterm and very preterm infants. Although IMR for very low birthweight infants increased, most of the increase in IMR from 2001 to 2002 was due to a change in the distribution of births by birthweight and, more specifically, to an increase in infants born weighing less than 750 grams. The majority of infants born at less than 750 grams die within the first year of life; thus, these births contribute disproportionately to overall IMR. Increases in births at less than 750 grams occurred fornon-Hispanic white, non-Hispanic black, and Hispanic women. Most of the increase occurred among mothers 20 to 34 years of age. Although multiple births contributed disproportionately, most of the increase in births at less than 750 grams occurred among singletons. Three hypotheses were evaluated to assess their possible impact on the increase in less than 750-gram births: possible changes in (1) the reporting of births or fetal deaths, (2) the risk profile of births, and (3) medical management of pregnancy. Although each of these factors may have contributed to the increase, the relative effects of these and other factors remain unclear. More detailed studies are needed to further explain the 2001-2002 infant mortality increase.