The clinical significance of bacteremia due to vancomycin-heteroresistant staphylococci and a rapid laboratory screening method were examined; 203 strains of staphylococci isolated from patients with clinically significant bacteremia were screened by the disk-agar method with use of vancomycin-salt agar to demonstrate satellitism around an aztreonam disk as well as by conventional population screening. Eighteen isolates (three Staphylococcus aureus and 15 coagulase-negative staphylococci) were shown to be heteroresistant to vancomycin. A case-control clinical study showed that the interval between admission and bacteremia, admission to the intensive care unit, prior use of vancomycin and/or beta-lactams, and isolation of methicillin-resistant staphylococci were significantly more common among patients with bacteremia due to staphylococci with heteroresistance to vancomycin; these patients had an overall mortality of 44.4%. The use of vancomycin and admission to the intensive care unit were independently significant risk factors on multivariate analysis. Vancomycin heteroresistance is inducible by salt and beta-lactams. Indiscriminate sequential use of beta-lactams and glycopeptides may facilitate the emergence of glycopeptide resistance.