Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations. Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone. No immediate side effects were noted. Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction. Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment. Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding. Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved. In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe. The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended.