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Objective. Because there is no evidence for the effectiveness of antibiotic prophylaxis in children with neurogenic bladder, the value of once-daily nitrofurantoin macrocrystals was assessed in a selected population with neurogenic bladder due to meningomyelocele. Methods and trial population. Children with significant urinary tract abnormalities other than neurogenic bladder were excluded. A urinary tract "infection" was defined as ≥108 colony forming units of bacteria/L of urine together with pyuria of ≥50 x 106 leukocytes/L, and/or symptoms consistent with an urinary tract infection. Fifty-six children participated in a 24-week double-blinded, placebo-controlled cross-over study. The infeclion status was assessed at two weekly intervals or if relevant clinical manifestations occurred. Results. For the whole trial the average percentage of "infections" per urine sample for each patient was reduced from 39% on placebo to 19% on single daily dose prophylaxis (P < .0003). For the first 12 weeks of the trial corresponding figures were 45% on placebo and 22% on prophylaxis (P < .0018). There was evidence for a marked carryover protective effect of nitrofurantoin into the placebo arm of the trial. Conclusion. Nitrofurantoin is an effective prophylactic agent during a 3-month period. Long-term studies are needed to confirm the reasonable expectation of a beneficial effect on urinary tract damage.