Vancomycin is often administered to hemodialysis patients at long dosage intervals because its removal by hemodialysis is considered to be negligible. We and others, however, have demonstrated significant removal of vancomycin by high-flux hemodialysis. This report describes our experience with 89 courses of vancomycin using a revised regimen with a loading dose followed by 500 mg doses after each dialysis treatment, and compares results with 41 courses using single weekly dosing. All patients were dialyzed with high-flux membranes using volumetric ultrafiltration and bicarbonate dialysate. Serum vancomycin levels were obtained two hours after completion of infusion (peak) and immediately prior to dialysis (trough) and were measured by Abbot TDx fluorescence polarization immunoassay. Duration of multiple-dose therapy was 11 +/- 8 days, with mean total dose 3.6 +/- 1.8 g. Initial doses of 20 mg/kg rapidly and reliably established therapeutic pre-dialysis serum levels (10 to 25 micrograms/ml). In patients treated with multiple dosing 431 pre-dialysis levels were obtained. The mean level was 15.9 +/- 5.7 micrograms/ml; 55 levels (13%) were less than 10 micrograms/ml and 22 (5%) were above 25 micrograms/ml. In patients treated once weekly, 77% of levels were below 10 micrograms/ml by five days after administration, and 84% at one week. No patient developed demonstrable ototoxicity. Twenty-five patients were treated for > or = two weeks, five for > or = four weeks, and two for > five weeks, with no evidence of toxic accumulation. Mean peak level was 20.1 +/- 4.6 micrograms/ml, with a mean difference from preceding pre-dialysis level of 7.2 +/- 2.2 micrograms/ml. We conclude that in high-flux hemodialysis, a 20 mg/kg loading dose of vancomycin followed by 500 mg doses after each dialysis treatment achieves predictable, adequate and safe therapeutic levels, does not lead to unacceptably high peaks, and does not accumulate during long treatment courses. By contrast, once-weekly vancomycin dosing resulted in subtherapeutic serum levels after five to seven days, and should be abandoned in the high-flux setting.