Résumé : In-vitro study of the combination of oxacillin with rifampicin has shown that a complex interaction occurs between the two drugs: a high oxacillin/rifampicin ratio was associated with antagonism, a low ratio was more likely to result in synergy - the combination acquired a higher rate of killing. Oxacillin significantly prevented or delayed the regrowth of rifampicin-resistant mutants, and antagonism for high oxacillin/rifampicin ratios only affected rifampicin-susceptible strains. The two clinical studies that we have performed suggested that the addition of rifampicin to standard treatment improved the clinical outcome of the patients with staphylococcal infections, and this was particularly true for the most severe infections. Failures were not associated with the emergence of rifampicin-resistant strains; the combination was not associated with more superinfections nor with more toxicity or intolerance. Serum bactericidal activities reflected a similar complex interaction to that observed in vitro by time-kill curves or checkerboard techniques. © 1984 The British Society for Antimicrobial Chemotherapy.