The authors report a prospective, randomized 18-month study on the effect of prophylactic antibiotic treatment in 152 hydrocephalic patients in whom clean shunt operations or revisions were done. The treated group received methicillin (totally 200 mg/kg) divided into six i.v. doses during 24 hours starting at the induction of anesthesia. Patients allergic to penicillin received erythromycin instead. Seventy-nine patients received antibiotics, and 73 (the control group) received none. All patients were followed at least 6 months after operation or to their death. Eleven patients developed signs of infection, giving an overall infection rate of 7.2%; however, the infection occurred less than 1 month after the operation in only half of these. Six of the patients had septicemia, 4 had peritonitis, and 1 had meningitis. In the treated group, the infection rate was 8.9%; in the control group, the rate was 5.5%. There was no statistically significant difference. The prophylactic antibiotic regimen in this investigation did not reduce the infection rate connected with cerebrospinal fluid shunting procedures.