Indomethacin has proven effective in closing the patent ductus arteriosus (PDA) in most low birth weight (LBW) neonates with this disorder. Early reopening of the ductus is a problem and often leads to the need for surgery. Prolonged use of indomethacin for several days has been suggested as a means to alleviate this problem. The present study was designed to determine if prolonged therapy over 5 days is more effective than a two-dose regimen in preventing reopening of the PDA. Seventy neonates were randomized for either prolonged therapy over 1 week or to receive two doses of indomethacin. All infants were given two doses of indomethacin 0.15 mg per kg, 12h apart. The maintenance group received an additional 0.1 mg per kg daily for 5 days. Ten days after the infants' initial dose of indomethacin, 6 of 22 in the nonmaintenance group as compared to 0 of 22 in the maintenance group had reopening of their ductus arteriosus. Ten infants in the maintenance group eventually had the ductus reopen at a median of 29, range 11-66 days compared to a median of 3, range 2-44 days in the nonmaintenance group. Significantly fewer babies in the maintenance group had a grade II-IV intraventricular hemorrhage compared to the nonmaintenance group. There was no other significant difference in the two groups in the incidence of necrotizing enterocolitis, retrolental fibroplasia or death. Indomethacin given over 5 days is effective for closure of the ductus arteriosus and will prevent reopening until after the acute clinical course in babies under 1500 g; however, the overall incidence of reopening was not different.