Metal sensitivity, as measured by an in-vitro assay on peripheral blood lymphocytes, was evaluated in patients with failed joint prostheses. Lymphocyte transformation to chromium, cobalt, and nickel was measured in 24 patients having revision surgery for a painful or loose prosthesis and compared with that in 11 patients who had a successful hip prothesis in situ for at least 2 years previously. A positive response (lymphocyte stimulation index greater than 3) to at least one of the metals was found in 71% of the revision group compared to 9% of controls (P < 0.01). The positive correlation between prosthesis failure and in-vitro metal sensitivity suggests that cell-mediated immunity to metals to metals may play a role in prosthesis failure. Furthermore, this simple in-vitro test may provide the basis of a useful diagnostic test for an often difficult clinical problem.