Phototherapy results in the conversion of native bilirubin to more water-soluble configurational and structural isomers. The serum half-life for the configurational isomer, the principal photoproduct in vivo, was determined by high pressure liquid chromatography in six premature infants following cessation of phototherapy. The mean half-life for this isomer was 15 h. The excretion of this isomer, calculated from the measured half-life, is less than half of daily bilirubin production, and therefore cannot account for the total bilirubin elimination observed during phototherapy. The serum concentration of the structural isomer, lumirubin, is lower than that of the configurational isomer; however, excretion is more rapid (serum half-life less than 2 h). Because of its rapid excretion, lumirubin may be an important pathway for bilirubin elimination during phototherapy.