To report possible red-man syndrome (RMS) associated with oral administration of vancomycin. A 23-month-old child with acute myeloblastic leukemia developed symptoms compatible with RMS while receiving oral vancomycin for suspected Clostridium difficile colitis. Serum concentrations of vancomycin, measured at the time of the clinical episode, demonstrated significant oral absorption of the drug. Serum concentrations of vancomycin decreased later, implying a possible decrease in absorption, after the patient's neutrophil count returned to normal. The child later experienced another clinical episode compatible with RMS while vancomycin was being administered intravenously for suspected sepsis. There is no published report of RMS following oral administration of vancomycin. The reaction described took place while the child was neutropenic. Because of the absence of any significant renal function alteration that could explain the importance of the serum concentrations observed, we assume that C. difficile, neutropenia-, and chemotherapy-associated colitis may have resulted in extensive intestinal lesions, leading to an increased amount of vancomycin being systemically absorbed. This increased absorption during profound neutropenia may have been sufficient to exceed a purported threshold, leading to RMS. This case demonstrates that significant absorption of vancomycin may occur in neutropenic patients with normal renal function, and that it may be accompanied by RMS, usually associated with rapid infusions or large parenteral doses of the drug.