Acetaminophen is the pharmaceutical most frequently ingested by small children. Although past research has allowed the safe management of 90% of these ingestions at home, several thousand are still referred to emergency departments annually. With the goal of further reducing the number of unnecessary referrals, the risk/benefit considerations of alternate referral strategies were analyzed. In a retrospective poison center chart review study from 11 centers, the records of children between the ages 1 and 6 years who acutely ingested acetaminophen and were referred to a hospital for determination of serum acetaminophen concentration in 1986 and 1987 were identified using the database of the American Association of Poison Control Centers. Risk of hepatic injury was assigned on the basis of the Rumack-Matthew acetaminophen toxicity nomogram. The cohort was stratified in terms of the amount ingested and whether a pediatric or adult preparation was ingested. The direct cost of an evaluation was estimated from four centers. Sensitivity, specificity and direct cost of each risk identification strategy were calculated. Eight hundred sixty six of 2091 patients had a timed serum acetaminophen concentration recorded. Of these, three patients had results in the "probable risk" area of the nomogram. A referral reduction strategy which would refer only children who ingest 200 mg/kg or more of an adult preparation could eliminate 82% of referrals without missing any of these "probable risk" patients. Six other children were determined to have serum acetaminophen concentrations in an area of the nomogram labeled "possible risk". No referral reduction strategy explored identified all of these patients. The average charge for an emergency department evaluation in 1992 was $272.00. These data suggest that children less than six years of age who ingest pediatric acetaminophen products other than those from packages containing greater than 30 tablets or who ingest less than 200 mg/kg of an adult preparation may be safely managed at home without referral to a hospital. This strategy would result in significant cost savings and prevent unnecessary inconvenience to many patients and families.