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During a double-blind placebo-controlled study, the effect of cloxacillin prophylaxis in craniotomies on samples taken for culture from 334 operation wounds in 279 patients was assessed. Patients and operations were equally divided over the cloxacillin and placebo groups. In the cloxacillin group significantly fewer samples contained microorganisms than was the case in the placebo group both just after the incision was made (p less than 0.05) and just before closure of the wound (p less than 0.001). The contaminating bacteria found most frequently were Propionibacterium acnes and Staphylococcus epidermidis. For material collected immediately after the incision, the percentage of cultures positive for S. epidermidis was significantly (p = 0.001) lower in the cloxacillin group than in the placebo group; the percentage of cultures with P. acnes did not differ between the two groups. For samples taken just before the wound was closed, the percentage of cultures with P. acnes or S. epidermidis was significantly (p = 0.008 and 0.003, respectively) lower in the cloxacillin than in the placebo group. In the placebo group neurosurgical infections occurred with P. acnes and/or S. epidermidis as causative microorganisms; in almost all cases those bacteria could be cultured from the edge of the wound. In none of the patients with an infection caused by S. aureus was the bacteria found in the operation area. In 2/6 infections in the cloxacillin group the infecting microorganisms could be cultured from the operation area. These findings support a significant reduction in the infection rate after craniotomy under cloxacillin prophylaxis compared with placebo.