Clinical isolates of Enterococcus faecium that had a range of susceptibilities to penicillin were found to differ significantly in their responses to the antibiotic. In the penicillin-susceptible group (MIC, ≤4 μg/ml), the cessation of growth (bacteriostasis) at 10x the MIC of penicillin appeared to correlate with the inhibition of penicillin-binding protein (PBP) 5*, whereas the onset of lysis (bactericidal effect) at higher antibiotic concentrations (100x the MIC) was concomitant with the inhibition of the lower-affinity PBP 5. In contrast, in the resistant (MIC, ≥8 μg/ml) group (in which most of the strains did not contain PBP 5*), the degree of saturation of PBP 5 seemed to determine the physiological response to the antibiotic: low levels of saturation caused growth inhibition, whereas almost complete saturation correlated with lysis. The penicillin-induced cell lysis of both penicillin-susceptible and -resistant strains was attributed, at least in part, to the extensive loss of acylated lipoteichoic acid into the growth medium.