The effects of acetoacetic acid, acetone, bilirubin, beta-carotene, three cephalospoprin antibiotics, glucose, hemoglobin and lipid on the kinetic Jaffé reaction and an enzymatic reaction for the determination of creatinine concentration were studied in bovine, canine, feline and equine serum. There were no obvious species' differences. The kinetic Jaffé reaction was unaffected by the addition of beta-carotene and hemoglobin. Acetone, cefazolin, cefoxitin, ceftiofur and glucose caused a positive bias while acetoacetic acid, bilirubin, and lipid caused a negative bias when added to the kinetic Jaffé reaction. The enzymatic reaction was unaffected by the addition of acetoacetic acid, acetone, beta-carotene, cefazolin, cefoxitin, glucose and hemoglobin while added lipid, bilirubin and ceftiofur caused a negative bias in the test results. Over all species and interferents, there was no difference in the precision of the two assay methods. In a series of sera from hospitalized patients, the two methods were highly correlated in a linear fashion. The enzymatic creatinine assay deals effectively with most interferents but has a greater cost and shorter shelf-life compared with the kinetic Jaffé reaction.