A controlled clinical study was set up to examine whether penicillin G sodium (PG) or ceftriaxone (C) is superior in the treatment of acute neuroborreliosis in childhood. Within a time period of 18 months 77 children with symptoms indicative of Lyme borreliosis of the central nervous system (CNS) were seen. In 23 of these childrenBorrelia burgdorferi specific cerebrospinal fluid (CSF) parameters confirmed the diagnosis of a neuroborreliosis. These children were treated at random with intravenous (i.v.) PG 400,000 – 500,000 I.U./kg/day for 14 days (group I) or with i.v. ceftriaxone 75–93 mg/kg/day for 14 days (group II), respectively. Clinical examination and a set of diagnostic laboratory parameters were done at admission, right after therapy, three, six and partly 12 months after therapy. The general condition of all children in both groups improved dramatically during antibiotic therapy, and no relapse occurred within the observation period. Considering the clear and comparable decrease ofB. burgdorferi serum titres and the clinical outcome (duration of disease and follow-up for at least six months) in children of both groups no difference between both antibiotic drugs can be demonstrated.