Twenty-one patients with rheumatoid arthritis received injections of either 40 mg or 80 mg of methylprednisolone acetate into one or both knee joints. Serum methylprednisolone and cortisol levels were measured at intervals up to 1 week following injection. Peak serum levels of methylprednisolone were reached at between 2 and 12 hours following injection, and increasing the injected dose resulted in correspondingly higher serum levels. Injection of 80 mg of methylprednisolone as 40 mg into each knee produced consistently higher peak serum levels than when given as a single intra-articular injection. Serum cortisol levels were substantially suppressed for up to 1 week, and this effect was seen at all dose levels.