Four patients are described with documented coccidioidal synovitis of the knee joint. In two of them, no previous diagnosis of coccidioidomycosis had been made prior to diagnosis of coccidioidal synovitis. The other two had active disease after courses of amphotericin B administered both parenterally and intra-articularly for disseminated coccidioidomycosis and coccidioidal synovitis. After synovectomy and limited parenteral amphotericin B therapy, none of the four patients show evidence of active synovial infection two to seven years later. Synovectomy appears to be an important aspect of the optimal therapy of coccidioidal synovitis of the knee, and when performed, the parenteral dosage of amphotericin B can be limited. Intra-articularly administered amphotericin B is also advocated when possible.