The in-vitro activities of cefmetazole, flomoxef, imipenem, vancomycin and enra-mycin alone and in combination with cefotiam against eighteen clinically isolated methicillin-resistant Staphylococcus aureus was investigated. Cefotiam, cefmetazole, flomoxef and imipenem inhibited the growth of clinical isolates at concentrations ranging from 100 to 1600, 6·25 to 400, 6·25 to 400 and 0·78 to 200 mg/L, respectively. Synergic effects were observed with combinations of cefotiam and cefmetazole, flomoxef or imipenem against more than 70% of the strains. The fractional inhibitory concentration (FIQ index values were less than 0·1. Vancomycin and enramycin alone inhibited the growth of all strains at concentrations ranging from 0·39 to 1·56 mg/L and 0·2 to 0·78 mg/L, respectively. Moreover, vancomycin and enramycin in combination with cefotiam showed synergy against strains in which no synergic effects were observed when cefotiam was combined with other β-lactam agents. About 50% of the strains tested were inhibited synergically by cefmetazole, flomoxef or imipenem, at clinically relevant concentrations in combination with 0·78 mg/L of cefotiam. The effects of vancomycin or enramycin in combination with cefotiam on the growth of a homogeneous resistant clone, which was derived from one of the clinical isolates, TS-65, was also studied. Regrowth in the presence of vancomycin or enramycin alone was suppressed when cefotiam was added.