Certain drugs are known to compete with bilirubin for albumin binding; therefore, all drugs administered to neonates should be tested to determine the degree of competition. The effect of cefmenoxime on bilirubin-albumin binding was determined by comparing the oxidation rate of free bilirubin in the presence and absence of drug. The reserve albumin concentration (RAC) of pooled cord serum was also measured using the MADDS dialysis rate method. We show that cefmenoxime competes with bilirubin for albumin binding with a displacement constant, of 3.1 x 10(3) l/mol. The maximal displacement factor (MDF) is used to determine the clinical effect of the drug at usual serum concentrations. The MDF for cefmenoxime is 1.10, representing approximately a 10% increase in free bilirubin concentration. In comparison, the MDF for a known bilirubin displacing drug, sulfisoxazole, is 2.43. The MADDS method showed an estimated 28% decrease in the RAC at 150 mumol/l, the mean peak serum concentration (MPSC) of cefmenoxime. These results show while cefmenoxime affects bilirubin-albumin binding, the degree of the effect is relatively small. However, cefmenoxime may pose a hazard to very sick, premature infants, especially if the infant is jaundiced.