Sisomicin is a new aminoglycoside antibiotic produced by the growth of a species of Micromonospora, M. inyoensis. The antibiotic is produced substantially as a single component and most closely resembles gentamicin C1a, a component of the gentamicin complex (C1, C1a, C2). Minimal inhibitory concentrations (MIC) of sisomicin appear less than of the other aminoglycosides. This new antibiotic has a spectrum of in vitro antimicrobial activity similar to that of gentamicin, however, it is more active particularly against strains of Pseudomonas aeruginosa and indole positive proteus. Bacterial strains resistant to gentamicin are usually resistant to sisomicin. In the presence of serum, sisomicin appears to be more bactericidal than gentamicin,andin in vivo mouse protection studies, it has been shown to be two to four times more effective. In mice, rats, and guinea pigs, the acute LD50’s for sisomicin are between one-half and three-fourths of those for gentamicin. In the cat, sisomicin appears to be slightly more vestibular toxic than gentamicin. Auditory toxicity studies in the guinea pig show that it is slightly less toxic than gentamicin, and based on the projective therapeutic dose, probably less toxic than kanamycin. Comparative studies of nephrotoxicity in the dog indicate that the nephrotoxic potential of sisomicin is similar to that of gentamicin. However, in the rat and cat, it appears to be slightly more nephrotoxic.