The novel lipopeptide antibiotic, daptomycin, at a concentration of 8 mg/L, caused gross morphological changes in both a methicillin-sensitive and a methicillin-resistant strain of Staphylococcus aureus and in a strain of Enterococcus faecalis. The earliest (after 1 h) surface lesion observed was the appearance of boss-like processes randomly distributed on the cell surface. Later, grossly deformed bacteria were seen and in two of the three bacteria prolonged exposure led to degeneration of the cells into an amorphous syncytial mass. Omission of calcium (which is known to potentiate the activity of daptomycin) from the culture medium did not affect the morphological response to an inhibitory concentration of the antibiotic.