Indomethacin is used in closure of the ductus arteriosus in newborn humans as well as in related research in near-term sheep and goats. Conflicting data in these studies have led to a reexamination of indomethacin stability. Solutions at various pH values, at two temperatures, and in polyethylene glycol (PEG-400), were assessed by high-pressure liquid chromatography for indomethacin and its products. Solutions below pH 7.4 were stable. Decomposition was rapid in alkaline solutions. Solutions at pH 7.4 showed no changes up to 24 h. Solutions of sodium indomethacin, and of indomethacin in PEG were stable. Solutions in aqueous Na2CO3 were variably stable depending on the mode of mixing. A solution prepared directly in 0.1 M Na2CO3 (pH 10.7) lost 75% of its content in 80 min; a similar solution diluted immediately with two volumes of pH 7.4 buffer (final pH 9.9) showed less decomposition. A solution in Na2CO3 adjusted to pH 7.4 with HCl was stable (at least 24 h). Solutions prepared by suspending indomethacin in 0.9% NaCl and adding Na2CO3 slowly were stable for 80 min; rapid mixing led to decomposition. Solutions in plasma were stable at −20 °C (2 months). Lack of indomethacin activity in some biological studies may have resulted from injection of inactive solutions.