The serum protein-binding of 12 representative cephems (CET, CEZ, CZX, CPZ, CZON, CPM, CDZM, CFX, CMZ, CTT, LMOX, FMOX) was assessed, using sera from young healthy subjects (mean age, 28.6 years old) and elderly healthy subjects (mean age, 69.7 years old), applying equilibrium dialysis under the same conditions in vitro. The protein-binding capacity of 12 cephems in elderly subjects was significantly less than that in young subjects, and marked increase in free drug concentration was observed in elderly subjects. This decrease in the protein binding capacity of cephems in elderly subjects was possibly caused by decreased serum albumin and change in non-esterified fatty acid constitution related to aging. As free-drug concentration participates in the appearance of effects and adverse reactions, the possibility of an enhanced pharmacological effects and increased adverse reactions of cephems due to decrease of protein binding in elderly subjects should be considered.