Twelve clinical strains of Staphylococcus haemolyticus (eight methicillin resistant and three methicillin susceptible), isolated from blood cultures between 1982 and 1997, were investigated for teicoplanin and vancomycin susceptibility profiles. On the basis of conventional MIC tests and breakpoints, four isolates were susceptible (MICs, 1 to 8 µg/ml) and eight were resistant (MICs, 32 to 64 µg/ml) to teicoplanin while all were susceptible to vancomycin (MICs, 1 to 2 µg/ml). All four strains for which the conventional teicoplanin MICs were within the range of susceptibility expressed heterogeneous resistance to teicoplanin and homogeneous vancomycin susceptibility. Of the eight strains for which the conventional teicoplanin MICs were within the range of resistance, six expressed heterogeneous and two expressed homogeneous teicoplanin resistance while seven showed heterogeneous vancomycin resistance profiles (with subpopulations growing on 8 µg of the drug per ml at frequencies of 10⁶ for six strains and 10⁷ for one) and one demonstrated homogeneous vancomycin susceptibility. Of six bloodstream isolates of other staphylococcal species (S. aureus, S. epidermidis, and S. simulans), for all of which the conventional teicoplanin MICs were 4 µg/ml and the vancomycin MICs were 2 µg/ml, none exhibited heterogeneous susceptibility profiles for teicoplanin while three showed homogeneous and three showed heterogeneous susceptibility profiles for vancomycin (with subpopulations growing on 8 µg of the drug per ml found for only one strain). The results of this study indicate that a heterogeneous response to glycopeptides is a common feature of S. haemolyticus isolates and suggest that susceptibility to glycopeptides as determined by conventional MIC tests may not be predictive of the outcome of glycopeptide therapy.