The bactericidal activity of azlocillin and piperacillin was tested at concentrations of 1/4 the MIC, the MIC and four-fold the MIC agents a serum-resistant Staphylococcus aureus and a serum-resistant Pseudomonas aeruginosa strain in broth, in serum and in the presence of leukocytes. The antibacterial activity of azlocillin and piperacillin in serum against Staphylococcus aureus was slightly better than in broth (p greater than 0.05); both compounds were distinctly less active against Pseudomonas aeruginosa in serum than in broth (p less than 0.05). Both antibiotics enhanced susceptibility of Pseudomonas aeruginosa to leukocyte killing without serum (p less than 0.05), whereas leukocyte killing of Staphylococcus aureus was hardly improved even at the MIC and four-fold the MIC of both compounds. The antibacterial activity of azlocillin and piperacillin against both bacterial strains was most pronounced in the presence of leukocytes and serum. A marked bactericidal effect was achieved at 1/4 the MIC, the effect not being further significantly enhanced (p greater than 0.05) at the MIC or four-fold the MIC.