Vancomycin pharmacokinetics in hydrocephalic shunt prophylaxis and relationship to ventricular volume. Vancomycin pharmacokinetics were determined in 25 patients receiving ventriculoperitoneal shunts for hydrocephalus. Computed tomography scan-derived ventricular-brain ratio as an expression of hydrocephalus varied between 9.3% and 15.4% (12.9% +/- 1.7%). One hour prior to surgery each patient received 1 g of vancomycin infused intravenously over 60 minutes. Samples of cerebrospinal fluid and venous blood were obtained 1 hour later and vancomycin levels assayed by fluorescence polarization immunoassay. There were 11 females and 14 males, with a mean age of 44.5 +/- 10.3 years and a mean weight of 72.0 +/- 11.4 kg. All had normal renal function. Levels of vancomycin in the cerebrospinal fluid at 1 hour ranged from 0.1 to 1.5 micrograms/mL (0.9 +/- 0.3). Weight did not affect these values (p greater than 0.1). Simultaneous blood vancomycin levels varied between 9.1 and 38.7 micrograms/mL (22.3 +/- 8.3). Ventricular volume, expressed as the ventricular-brain ratio, did not correlate with cerebrospinal fluid vancomycin levels (p greater than 0.5). There was no significant increase in concentrations of vancomycin in CSF as cerebrospinal fluid protein concentration increased, nor when blood vancomycin concentration was greater than 20 mg/dL (therapeutic range) (p greater than 0.1). No patient had evidence of infection at 6 months follow up. These results indicate minimal cerebrospinal fluid penetrance of vancomycin when administered systemically 1 hour prior to shunt surgery. In addition concentrations of vancomycin in cerebrospinal fluid bear no relationship to weight, ventricular volume, meningeal inflammation, or blood levels in the therapeutic range. The minimum inhibitory concentration of vancomycin for staphylococci is 1.5 to 3.1, and as bactericidal levels of 5 to 8 minimum inhibitory concentration are needed to kill organisms, a combination of both systemic and intraventricular vancomycin may be needed to ensure adequate cerebrospinal fluid and tissue concentration of antibiotic during shunt prophylaxis. 