In the present study we investigated quantitatively the incidence of hypoplasia of the arcuate nucleus (ARCn) of the medulla oblongata, reported earlier [Gozal D, Hathout GM, Kirlew KAT (1994) J Appl Physiol 76:207], as well as its distribution in 62 cases of sudden infant death syndrome (SIDS; mean age 14 postnatal weeks, 39 male and 23 female) and 25 controls (mean age 16 postnatal weeks, 14 male and 11 female), using detailed histopathological and morphometric analyses performed on serial sections of medulla oblongata. The SIDS cases were divided into four subtypes: SIDS A (27 cases, 43%) with histologically well-developed ARCn; SIDS B (16 cases, 26%) with severe bilateral hypoplasia along the whole length; SIDS C (11 cases, 18%) with partial bilateral hypoplasia, located mainly in the lateral portions of the caudal two thirds of the nucleus, and SIDS D (8 cases, 13%) with right monolateral hypoplasia of the ARCn. ARCn hypoplasia was detected in 56% of cases (35 cases). Three-dimensional volume reconstruction showed that in the SIDS A victims the mean volume was analogous to controls, whereas in the SIDS group with ARCn hypoplasia, severe or partial, the mean volume was significantly different from controls on both sides of the medulla oblongata (SIDS B group: P=0.003, P=0.002; SIDS C group: P=0.007, P=0.008). The mean ARCn volume in the SIDS D group was statistically significant only on the right side ( P=0.005). We also observed reduced neuron density of the ARCn, associated with a decrease in the total number of neurons over the whole length of the nucleus itself. On the basis of the morphometric results of neuronal population in the different portions of the ventrolateral medulla in SIDS cases, we hypothesized that infants without the full complement of neurons and neuropil (ARCn hypoplasia) are at risk for SIDS because they are unable to develop appropriate cardioventilatory control during this crucial developmental period.