Amide penicillin Wy-12,556 and DBED penicillin were studied for their antibacterial effect in CD-1 mice repeatedly infected with Streptococcus pyogenes C203 and/or Staphylococcus aureus Smith. Animals infected with S. aureus Smith failed to show a difference between the therapeutic activity of DBED penicillin and Wy-12,556. Wy-12,556 was significantly more effective than DBED penicillin in protecting the animals challenged repeatedly with S. pyogenes C203. Wy-12,556 provoked a positive transient chemotactic response in uninfected mice. 24 h after intraperitoneal challenge the exudate showed a high neutrophilic count.