To determine the effects of a single session of intraarticular methylprednisolone (IA-MP) injections on the function of the pituitary-adrenal axis. Twenty-five patients with rheumatic diseases were treated with a single IA-MP injection. The dose varied between 20 and 160 mg. The basal cortisol level and the response to 1 microg adrenocorticotropic hormone (ACTH) stimulation were determined before treatment, at 1 day, and at 1 week after IA-MP injections. Further tests were carried out for up to 6 weeks in patients with blunted cortisol response. Results were compared with those obtained in a group of 22 healthy subjects. Before treatment, all patients had normal basal and peak cortisol responses to ACTH (>396 nmoles/liter at 30 minutes). Reduced fasting cortisol levels (<147 nmoles/liter) were detected in 12 of 25 patients (48%) after 1 day, in 1 of 25 patients (4%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Blunted peak cortisol response (<396 nmoles/liter at 30 minutes) was observed in 1 of 25 patients (4%) after 1 day, in 3 of 25 patients (12%) after 1 week, and in 1 of 25 patients (4%) 2 weeks after IA-MP injections. Decreased fasting levels and peak cortisol responses to ACTH stimulation were more common in patients with inflammatory diseases and in those injected with 80-160 mg MP. Single-session IA-MP injection(s) are associated with systemic absorption of MP, causing impaired adrenocortical reserve. Recovery is expected in most patients after 1-2 weeks. Only a few patients exhibited suppression for up to 2 weeks. The magnitude of this suppression depends on the dose injected, and is more common in patients with inflammatory joint diseases. Caution is required if repeated large doses of IA-MP are considered in these patients.