To assess the susceptibility of human beings to the neurotoxic effects of hexachlorophene demonstrated in experimental animals, a blind clinicopathologic analysis was made of 248 children coming to autopsy over a 7.5-year period in the two Seattle institutions to which practically all premature or sick children are referred. Repeated whole-body bathing of premature newborn infants in 3% hexachlorophene-bearing soap (undiluted pHisoHex) is associated with a vacuolar encephalopathy of the brainstem reticular formation. The prevalence of the vacuolar encephalopathy appears to be related to the number of exposures to hexachlorophene, to the concentration of hexachiorophene, to the birth weight (gestational age), to the length of survival and to the thoroughness of rinsing. From these observations we conclude that hexachlorophene should not be used on neonates under 1,400 gm birth weight and should be used only sparingly in full-term neonates with thorough rinsing.