The intramuscular administration of polymyxin B sulfate (PBS), polymyxin B methanesulfonate (PBMS) or colistin methanesulfonate (CMS) at 2.2 mg/kg/l2 h for 9 days to normal dogs did not produce physiologically significant alterations in glomerular filtration rate, renal plasma flow, tubular maxima for p-aminohippurate or glucose, or blood urea nitrogen. Depression of renal function did occur, however, in one of two dogs given CMS at 2.2 mg/kg/6 h (8.8 mg/kg/day) for 9 days. Clinical signs of hyperthermia, depression and pain at injection sites were seen only in dogs treated with PBS or with the high dosage regimen of CMS. Accumulation of antibiotic in the plasma did not occur with normal dogs on prolonged administration or in dogs whose kidneys were damaged with uranyl nitrate. A slow rate of plasma disappearance did occur, however, following the administration of PBS to a dog with glomerular amyloidosis. A dosage schedule for CMS of 1.1 mg/kg/6h (4.4 mg/kg/day) is recommended for clinical use in dogs on the basis of effective antibiotic concentrations produced in the plasma and urine and the absence of renal toxicity associated with this total daily dosage.