The purpose of this study was to assess the effect of a single dose of cephalexin on the pharmacokinetics of metformin in healthy human volunteers. A 2 x 2 double blind randomized crossover study was conducted in 12 healthy human volunteers. Each subject received orally either 500 mg of metformin with a placebo or a combination of 500 mg of metformin and 500 mg of cephalexin. Serum and urine levels of metformin were estimated by a validated HPLC method. The systemic disposition of metformin was altered by the co-administration of cephalexin. Cephalexin increased Cmax and AUC by an average of 34% and 24%, respectively, and reduced renal clearance to 14%. The renal clearance of metformin was reduced in a time-dependent manner in the presence of cephalexin. Hence, it is concluded that cephalexin inhibits the renal tubular secretion of metformin resulting in higher circulating serum concentrations.