The effect of semistarvation on the toxicity and ototoxicity of tobramycin sulfate (TO) and gentamicin sulfate (GE) was investigated in guinea pigs by electrophysiological and histopathological methods. The presented data has shown that the toxicity and ototoxicity of aminoglycoside antibiotics is substantially increased when guinea pigs were semistarved. Our results should also warn researchers using semistarvation in their conditioning experiments which investigate the toxicity of different chemicals. Toxicity was greater in GE- than TO-treated animals, which caused the GE-treated animals to die during treatment or shortly after treatment. Thus, TO should be preferentially used because it has been shown to be less toxic and ototoxic in normal and altered nutritional conditions.