Delays in antimicrobial therapy in high-risk patients with infection may have deleterious effects on clinical outcomes. Therefore, appropriate treatment must be initiated promptly. The objective of this prospective study was to determine the better loading dose of vancomycin in critically ill patients with suspected Gram-positive infections. Two groups of patients were studied successively: Group A, loading dose of 500 mg; and Group B, loading dose of 15 mg/kg. The mean post-loading dose serum vancomycin concentration was significantly higher in Group B than in Group A (19.1 +/- 7.4 mg/L versus 10.4 +/- 2.7 mg/L; P < 0.001), without producing toxic peak levels. Clinical cure rates were significantly different for infected patients in Group B compared with Group A: 93% (14 of 15 patients) versus 56% (10 of 18 patients), respectively. However, the proportion of patients surviving to Intensive Care Unit discharge was similar. Because vancomycin is believed to achieve maximum killing at concentrations in serum of four to five times the minimum inhibitory concentration for the infecting organism, our results suggest that the 15 mg/kg loading dose should be preferred.