In patients with pleural effusions due to malignant disease, estimations of ampicillin were made on simultaneously obtained samples of blood and pleural fluid: (1) from patients (n=11) after the administration of a single dose of 400 mg of bacampicillin, and (2) from patients undergoing treatment with 800 mg of bacampicillin twice daily (a) during the 12 hours after the first dose (n=10) and (b) during the 7 hours after the third dose (n=9). Bacampicillin gave concentrations in the pleural fluid well above the MIC of common pathogens including H. influenzae. Mean peak levels were 1.2 microgram/ml after the 400 mg dose and 3.8 microgram/ml after the first and third doses of 800 mg. The peak appeared later in the pleural fluid in comparison with serum peak levels. The elimination half life was considerably longer in the pleural fluid.