The prolonged biological half-life of Ceftriaxone, allowing once-daily dosing, has contributed to the large diffusion of this third-generation cephalosporin in children. Ceftriaxone is known to induce reversible precipitates in the gallbladder of adults and children. A prospective study was conducted during 1997 in 34 children admitted for the treatment of acute pyelonephritis. Ceftriaxone (intravenous daily single-dose of 50 mg/kg under 2g/day) was initially used. A first gallbladder sonogram, performed before the first or second injection, was normal in all cases. A second evaluation was performed before the fifth and last injection. On this second evaluation the presence of one (n = 3) or two gallstones was recorded in 5 children (15%) on a sonogram made after 3 (n = 4) or 5 (n = 1) injections. Their median age was 7 years (range 4 months to 11 years). All five children remained symptom-free and the normalization of the sonographic patterns was constant on the last sonogram performed 2 (n = 1), 3 (n = 2) and 5 months (n = 2) after discontinuation of Ceftriaxone. This study confirms the possibility of precocious biliary lithiasis under Ceftriaxone therapy in childhood and their spontaneous dissolution after discontinuation of the drug. They seem unpredictable and independent of the age, sex in a cohort homogeneous for the nature of the infection, modality of a short- and low-dose therapy. Clinicians and radiologists should be aware of this complication as an etiology of a so-called primary cholelithiasis and to prevent anxiety or unnecessary cholecystectomy. The antibacterial and pharmacokinetic benefits of Ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.