The passage of mezlocillin into the CSF was investigated in normal dogs and in dogs with experimentally induced Staphylococcus aureus meningitis. The areas under the curves (AUC) of mezlocillin concentrations in blood and CSF were compared. The antibiotic was administered by slow (1 hour) intravenous infusion in doses of 100, 200 and 400 mg/kg bodyweight. Samples of blood and CSF were collected simultaneously 30, 40, 60, 75, 90, 105, 120, 180 and 240 minutes after the infusion. The penetration of mezlocillin into the CSF of dogs with non-inflamed meninges was poor (peak less than or equal to 2 micrograms/ml, CSF/serum AUC ratio : 0.9 %), but it was very substantial in dogs with meningitis. After the 200 mg/kg dose, the mean CSF peak was 43 micrograms/ml (range : 33-60 micrograms/ml) and the CSF/serum AUC ratio was 26.6 %. Similar experiments were performed with other beta-lactam antibiotics. In dogs with healthy meninges the CSF/serum AUC ratios were 0.52 % with amoxycillin, 0.75 % with cefuroxime, 1.05 % with cefamandole, 1.18 % with cefoxitin and 3.6 % with cefotaxime. In dogs with meningitis, the corresponding ratios were 16.3 % with cefotaxime, 17.4 % with cefamandole, 18.5 % with cefoxitin, 18.6 % with amoxycillin and 18.7 % with cefuroxime. These results suggest that cefotaxime penetrates best across normal meninges and mezlocillin across inflamed meninges.