The effects of short-term food deprivation on the serum and renal distribution and nephrotoxicity of tobramycin were studied in female Sprague-Dawley rats maintained on a 14-h light/10-h dark cycle (light on: 06:00). For the distribution study, a single injection of tobramycin (40 mg/kg, i.p.) was administered at 14:00 or 02:00 to normally fed animals or to animals fasted for 12 h before tobramycin injection; these treatment times correspond to the peak and trough of tobramycin nephrotoxicity as previously determined in other studies. The serum and cortical levels of tobramycin were significantly higher 60, 120, and 240 min after the injection in fasted animals treated at 02:00 compared with normally fed animals treated at the same time (p < 0.05). In animals injected at 14:00, similar levels of tobramycin were measured in both fasted and fed rats. In the nephrotoxicity study, female Sprague-Dawley rats were fasted for 12 h before and 24 h after the timed single injection of tobramycin (150 mg/kg, i.p.). The 24-h urinary excretion of beta-galactosidase was significantly higher in fasted animals treated at 02:00 than in fed rats treated at the same time of day. Seventy-two hours following tobramycin injection, serum creatinine levels and cortical levels of tobramycin were significantly higher in fasted rats treated at 14:00 than at 02:00 and in fed rats treated at 14:00. These data suggest that a short period of food deprivation modulates the temporal variations of tobramycin nephrotoxicity.