Despite improvements in the care of preterm infants, intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PHH) continue to be frequent occurrences in this patient population. Shunt procedures in these children are frequently complicated by obstruction and/or infection. As the hydrocephalus is usually caused by an obliterative arachnoiditis due to contact of the blood with the basilar meninges, it was postulated that infusion of urokinase into the ventricles of infants who have sustained an IVH would clear the blood, mitigate the arachnoiditis, and prevent the progression of PHH. Accordingly, 18 preterm infants who had sustained IVH and subsequently developed PHH were treated with intraventricular urokinase instilled via a surgically implanted subcutaneous reservoir. There were no complications associated with the urokinase. Infants were divided into two dosage groups: low dose (110,000-140,000 IU total) and high dose (280,000 IU total). One infant in the low-dose group died at 1 month of life of respiratory complications. In the low-dose group, 3 of 8 (37%) infants required shunt placement; in the high-dose group, all 9 required shunt placement. For the total group, the shunt rate was 71%. This compares to a historical control group shunt rate of 92%. While the difference between the treatment group as a whole and control group approaches, but does not reach, statistical significance (p = 0.068), there was a significant reduction in the shunt rate when the low-dose group was considered separately (p < 0.002). For those infants that required shunt placement, there were fewer shunt revisions performed in the treatment group than in the control group during the first 24 months following shunt placement: 0.67 versus 1.5 shunt revisions/shunted child. Initial experience with intraventricular urokinase following IVH and PHH in preterm infants suggests a beneficial effect in reducing the shunt revision rate in both high- and low-dose groups. Reduction in shunt placement rate is seen only in the low-dose group.