Sepsis-related refractory hypotension may be mediated in part by endorphins. Naloxone (NLX), an endorphin antagonist, has been used as a treatment for hypotension in adults. Severe hypotension in neonates is sometimes refractory to the usual treatments including fluid boluses, dopamine, dobutamine, and epinephrine. To determine under what circumstances NXL is effective in neonates, we conducted a retrospective chart review of neonates admitted to our NICU from January, 1992 - November, 1996. Eleven neonates were identified who received NXL as an antihypotensive. Data collected included gestational age at birth, post conceptional age (PCA) at treatment, mean blood pressure (6h prior until 48h after initiation of NXL), dose of NXL, duration of shock prior to treatment, diagnosis, use of other antihypotensive agents or bolus fluids. Hypotension was defined as mean BP in mm Hg < PCA in weeks. Outcome was evaluated as BP response (increase in BP>10% above baseline or no further requirement for fluid boluses or other antihypotensives) and survival to discharge. Of 11 patients, 2 (who responded with increased BP) were excluded since they had normal baseline BP. Of the remaining 9, 7 responded to NXL and 6 survived. Both nonresponders died. The mean dose of NXL was 3.2 mg/kg and duration of NXL infusion 37.5 h (6h - 7d). Response was irrespective of PCA (26-38 weeks), duration of shock (6-168 h), diagnosis (sepsis, presumed sepsis). Our data suggest that naloxone is an effective antihypotensive in both term and preterm neonates and that failure to respond to NXL carries a poor prognosis for survival.