The course of 1,487 patients with myasthenia gravis followed between 1940 and 1985 for a mean of 18 years provides further evidence that the distribution, severity, and outcome of the disease are determined during the first 1 to 3 (occasionally 5) years after onset, suggesting that injury to acetylcholine receptors occurs mainly during this time. In 14%, the disease remained clinically localized to the extraocular muscles, and in the remaining 86% became generalized, in 87% within a year, with the disease reaching maximum severity within the first year after onset of symptoms in 55%, during the first 3 years in 70%, and during the first 5 years in 85%. Male patients tended to have more rapid progression of disease, higher mortality, and lower rates of remission and improvement than females. From 1940 to 1957, when management relied on anticholinesterase compounds, endotracheal intubation or tracheostomy and negative pressure assisted ventilation for respiratory failure, and thymectomy in 26% of patients and thymomectomy in 8%, 31% of patients with generalized myasthenia gravis died of the disease (29% of these during the first year after onset, 27% during the second and third years, and 17% during the fourth and fifth years), 32% improved, 23% remained unchanged, 10% went into remission, and only 5% were worse during the last year seen than during the worst of the first 3 years (or 5 years in the minority of patients who reached maximum weakness after 3 years). From 1958 to 1965, during which time the management of respiratory failure was improved by positive pressure and volume controlled ventilation and improved intensive care, mortality fell to 14% (p less than 0.005), and a higher proportion remained unchanged (p less than 0.005). From 1966 to 1985, when over half the patients received adrenal cortical steroids, mortality fell to 7% (p less than 0.005) and the proportion who improved rose to 47% (p less than 0.05). Even though the patients who received steroids usually had more severe myasthenia, they had a higher rate of improvement than those who received no steroid, 54% compared to 39% (p less than 0.005). Thymectomy was performed in one-fourth of patients with generalized myasthenia gravis, more frequently in young females and those with more severe weakness, and less often in older males and those with less severe weakness.(ABSTRACT TRUNCATED AT 400 WORDS)