Iophenoxic acid increases the fluorescence of bilirubin bound to human serum albumin at drug/albumin molar ratios lower than 1, while iopanoic acid decreases it. The fluorescence enhancement results probably from a change in the fluorescence efficiency due to an iophenoxic acid-induced conformational change in the albumin, which in turn causes displacement of bilirubin from the protein. Iophenoxic acid does not affect the high-affinity bilirubin binding site of albumin. Therefore any enhancement in bilirubin fluorescence caused by the drug indicates that bilirubin is bound to the low-affinity binding sites of albumin. The use of iophenoxic acid in the determination of the extent of saturation of the high-affinity bilirubin binding site of albumin may be of value in the clinical management of infants with neonatal jaundice.