We investigated the transpleural penetration of lomefloxacin (LFLX) and ceftriaxone (CTRX). LFLX (200 mg) was administered orally to three patients with transudative fluid and four with exudative fluid, and 2 g of CTRX was administered by drip infusion to four patients with transudative fluid and three with exudative fluid. For both groups that received LFLX and CTRX, blood samples were drawn at time zero and 1, 2, and 6 h after drug administration. Thoracocentesis of each group was performed at 6 h after drug administration. The mean ratios of concentrations in pleural fluid/maximum concentrations in serum (P/S max) of LFLX were 66% in patients with transudative fluid and 69% in patients with exudative fluid. The mean ratios of P/S max of CTRX were 9.1% in patients with transudative fluid and 13.5% in patients with exudative fluid. The P/S max ratios for the penetration of LFLX were five to six times higher than those for CTRX. In addition, there was less differentiation in concentrations of LFLX in pleural fluid between the transudative and exudative effusions than there was in the concentrations of CTRX.