Single doses of cefazolin, 500 mg intramuscularly and 1 g intravenously, were administered to 16 patients having lung pathology who were scheduled for thoracic fluid aspiration. Pleural fluid and serum samples were taken at intervals of 30 to 240 min for determination of cefazolin levels. The levels obtained were variable; however, the levels of cefazolin in pleural fluid generally exceeded the reported minimal inhibitory concentration values for Staphylococcus pneumoniae and Staphylococcus, and group A beta-hemolytic streptococcus. In addition, the pleural fluid levels exceeded the minimal inhibitory concentration for cefazolin against most of the Klebsiella and Haemophilus influenzae strains. These data show that cefazolin, despite its comparative high protein binding, produces levels in the pleural fluid capable of inhibiting the organisms commonly found in respiratory tract infections.