Volume expansion is used commonly in preterm infants to treat presumed hypovolaemia. However, the amount that should be given is uncertain. We present data that were obtained from anonymised regional case notes of Project 27/28, a national case-controlled study run by the Confidential Enquiry into Stillbirths and Deaths in Infancy. Various clinical parameters were analysed, including the volume expansion administered during the first 48 h of life. All deaths in the first year of the study in the West Midlands (cases, n = 22) and matched regional controls (survivors, n = 29) were included. The primary outcome was death within 28 days. Sixteen of the 22 deaths were considered 'not inevitable' on the basis of the neonates' condition at birth. These newborns received on average more than twice the volume expansion compared with controls in the first 48 h of life (38.2 vs. 18.2 mL/kg, P = 0.007). There were no significant differences between the groups in lowest blood pressure or base deficit within the first 12 h of life. Newborns who received >or= 30 mL/kg volume expansion in the first 48 h of life were more likely to die than those who received < 30 mL/kg (OR 4.5 [95% CI 1.2, 17.2]). Our data suggest that administration of >or= 30 mL/kg volume expansion is associated with increased mortality in neonates of 27-28 weeks' gestation. Unless there is clear evidence of hypovolaemia, clinicians should exercise caution when prescribing volume expansion.