Whole bowel irrigation, routinely used before colonoscopy, is evaluated as a potential gastrointestinal decontamination procedure for acute drug overdose. Nine adult volunteers, who served as their own controls, each ingested 5.0 g of ampicillin trihydrate on two occasions, one week apart. Whole bowel irrigation with polyethylene glycol electrolyte lavage solution was performed one hour after one ingestion. Serial serum ampicillin levels, electrolytes, osmolalities, body weights, and hematocrits were obtained. The areas under the concentration vs time curves for ampicillin were computed for both groups, and their means were compared. Mean duration of the procedure was 234 minutes and mean volume of infused polyethylene glycol electrolyte lavage solution was 7.7 L. Whole bowel irrigation produced a 67% decrease in ampicillin absorption and there were no significant changes in body weight, hematocrit, serum electrolytes, or osmolality. We conclude that whole bowel irrigation is an effective and safe gastrointestinal decontamination procedure for acute drug ingestion.