Long-term use of corticosteroids (CSs) may result in an increased risk of disseminated varicella. Concurrent administration of troleandomycin (Tao) to treat CS-dependent asthmatics can potentiate steroid effects. We present the first case of fatal varicella in a patient concurrently receiving methylprednisolone and Tao therapy. At the time of her death she had been receiving CSs for 2 years and Tao for 1 year. She had a 2-day history of fever, lower back and abdominal pain, dysuria, and constipation. Later, when pox lesions were evident, it was learned she had been exposed to varicella 2 weeks previously. While hospitalized she developed hepatitis, gastrointestinal hemorrhage, disseminated intravascular coagulopathy, and pneumonitis, resulting in respiratory failure. She succumbed despite treatment with stress doses of steroids, intravenous acyclovir, fresh frozen plasma, and ventilatory support. Autopsy findings revealed evidence consistent with disseminated varicella. This case suggests that concurrent therapy with CSs and Tao may increase the risk for disseminated varicella, possibly by enhancing CS-induced immunosuppressive effects. We suggest that other immunologic parameters in addition to serum varicella titers might be helpful in identifying those CS-dependent patients at risk. Any CS-dependent asthmatic, whether or not receiving Tao, should receive varicella-zoster immune globulin within 96 hours of exposure and acyclovir once varicella is clinically apparent. Varicella vaccine should be considered for those not yet exposed.