Asthma mortality is rising and noncompliance may be a contributing factor to asthma deaths. We have established a comprehensive treatment program for our most severe asthmatic patients, who are also noncompliant. The objective was to evaluate the effect of a treatment protocol for patients with malignant potentially fatal asthma on both clinical outcome and inpatient costs. A retrospective chart review of eight patients diagnosed with malignant potentially fatal asthma was conducted. Patients were initially evaluated in consultation either at Northwestern Memorial Hospital or in the Allergy-Immunology Clinic at Northwestern Medical Faculty Foundation. The patients all met at least one of the criteria for potentially fatal asthma and each patient was noncompliant with medical care, as they did not follow their doctor's instructions, did not keep scheduled appointments, and/or did not take prescribed medications. A treatment program that included regularly schedule visits with the same attending physician and physician in training, patient and family education, 24-hour telephone access, adequate doses of anti-inflammatory medication and psychiatric referral, if indicated, was instituted. The number of admissions to the hospital including intensive care unit admissions and emergency room visits was tabulated, as was the total cost per year per patient for hospital treatment of asthma before and after starting the treatment program. The number of hospitalizations markedly declined, with three of the eight patients requiring no further admissions to the hospital and three additional patients not requiring admission for at least 4 years. There were no fatal events and no further intensive care unit admissions. The mean cost per person per year for in-patient care before intervention was $22,999 +/- $20,639 and the mean postintervention cost per patient per year was $1107 +/- $1618. This was a statistically significant cost savings (P < 0.0017). We developed a comprehensive treatment program that has enabled us to successfully and cost effectively treat patients with malignant potentially fatal asthma.