Fifty-six cases of De Quervain's tenosynovitis (in 55 patients) were treated with a "long-acting" corticosteroid, methylprednisolone acetate, and followed prospectively over a 4-year period. Approximately 90% of these patients were effectively managed either with a single injection (58%) or with multiple injections (33%) of this compound. Seventeen patients experienced recurrence a mean of 11.9 months after the initial injection. Three had minor flares and were not reinjected; the others responded to reinjections. Ten percent of the cases could not be controlled with local injection, and these patients were referred for surgery. Adverse reactions were self-limited and relatively minor; no tendon ruptures or local infections occurred. We present a discussion of our review of the literature regarding medical therapy and surgical release for this condition. Treatment of De Quervain's tenosynovitis with methylprednisolone acetate injection rapidly controls the signs and symptoms, does not lead to serious adverse reactions, and should be the preferred initial treatment.