A patient with severe nocturnal asthma of multifactorial pathogenesis with high-risk features leading to several episodes of nocturnal respiratory arrests is described. Despite aggressive conventional therapy with bronchodilators and glucocorticoid agents, the patient had progressive worsening within the year prior to admission. After a nonconventional approach consisting of: high-dose inhaled steroids, afternoon dose of prednisone, addition of troleandomycin therapy, high-dose inhaled ipratropium at bedtime, maximizing serum theophylline concentrations in the early morning, and nasal CPAP through the night; the patient's pulmonary functions were optimized with minimal or no reduction in morning FEV1, and decreased airways hyperresponsiveness to methacholine.