The narrow therapeutic/toxic ratio of existing aminoglycosides has led to a search for safer drugs of this class. Isepamicin is a semi-synthetic aminoglycoside with a significantly low nephro as well as ototoxicity in animals and which is expected to have a clinical efficacy comparable to that of amikacin. We therefore compared its antibacterial activity with amikacin against 817 recent clinical isolates of gram-positive and gram-negative bacteria. The in vitro activity of isepamicin was comparable or slightly greater than amikacin against Staphylococcus aureus and most Enterobacteriaceae. However, it was significantly more inhibitory towards Serratia marcescens, Enterobacter and Klebsiella pneumoniae.