The nephrotoxicity of cephaloridine, cefazolin and mercuric chloride was studied in rabbits of various ages. Cephaloridine produced dose-related elevations in serum urea nitrogen, creatinine and renal tubular necrosis in adult and 30-day-old rabbits, only slight changes at 15 days of age and no effect in 5-day-old rabbits. Cefazolin also produced dose-related nephrotoxicity in adult rabbits but no effect in 15-day-old rabbits. Mercuric chloride administration resulted in similar nephrotoxicity in 5-, 15- and 30-day-old rabbits and adults. The development of susceptibility to cephaloridine nephrotoxicity paralleled the maturation of the renal anionic transport system as determined by the accumulation of p-aminohippurate by renal cortical slices in vitro. Substrate stimulation of the anionic transport system by p-aminohippurate or penicillin increased the nephrotoxicity of cephaloridine in between rabbits. The authors concluded that the lack of cephaloridine nephrotoxicity in newborn rabbits is due to the incomplete development of the renal anionic transport system.