The response to daptomycin of three strains of Staphylococcus aureus (one of which was methicillin-resistant) and a strain of Enterococcus faecalis was investigated by continuous turbidimetric monitoring. Daptomycin caused partial inhibition of bacterial growth at concentrations well below those suppressing growth overnight. The activity of the drug was more than 200-fold greater in the presence of a physiological concentration of calcium (2.5 mmol/l) than in its absence. Variants present in cultures inhibited by daptomycin were shown to exhibit decreased susceptibility to the drug and the susceptibility declined further on repeat exposure; however, there was a slow but incomplete reversion to susceptibility on sequential subculture in drug-free broth. Resistance was difficult to induce when the concentration of calcium in the broth exceeded 2.5 mmol/l.