The effect of sulfisoxazole, sodium salicylate, sodium cholate, urea and dimethyl sulfoxide on the kinetics of the bilirubin to human serum albumin at 24 degrees C and pH 7.40 was investigated. A marked decrease of the association constant was obtained. It was due mainly to that of the association rate constant, and might be an additional risk factor to the icteric newborn: when blood bilirubin increases, unbound bilirubin which cannot rapidly associate to albumin may reach a dangerous level, even when its equilibrium concentration is low.