Thirty-eight patients with severe mixed bacterial infections were treated with clindamycin and gentamicin. In vitro, all staphylococci and streptococci (other than enterococci) and 96% of anaerobes were susceptible to clindamycin; all staphylococci and 92% of Enterobacteriaceae and Pseudomonas aeruginosa were susceptible to gentamicin. Enterococci were usually resistant to both antibiotics. Significant synergy was only occasionally observed with this combination of antibiotics; there were no instances of antagonism. Among the patients treated with both drugs, there were four patients with pneumonia and empyema, 15 with infections of the skin, soft tissue, and/or bone, and 19 with intraabdominal infection. Nine patients had bacteremia, and 29 had failed to respond or had developed infections during previous antibiotic therapy. The results of treatment with clindamycin and gentamicin were considered to be excellent: 30 patients were cured, four improved, and four failed to respond. Concentrations of clindamycin in serum greatly surpassed minimal inhibitory concentrations (MICs) of clindamycin-susceptible pathogens; these organisms were eradicated from foci of infection. Concentrations of gentamicin in serum did not consistently surpass MICs for gentamicin-susceptible pathogens; these organisms and enterococci often persisted in foci of infection. In patients with complicated infections that required prolonged courses of treatment, Enterobacteriaceae, Pseudomonas aeruginosa, and enterococci occasionally emerged as predominant pathogens. Adverse reactions frequently occurred but were mild and reversible; treatment was discontinued in only two patients who developed rashes.