Four adult patients with chronic mucocutaneous candidiasis were studied to establish a possible role for cimetidine as an immunomodulator. These patients had negative baseline in vivo and in vitro cell-mediated immune response to Candida antigen as measured by intradermal skin tests, lymphocyte transformation and leukocyte migration inhibitory factor production to Candida antigen. Patients were given a 4-wk course of cimetidine, 300 mg by mouth, 4 times daily. Subsequently 4 of 4 patients developed strong (> 15 mm) intradermal skin test reactions, and 2 of 4 patients produced leukocyte migration inhibitory factor to Candida antigen. Skin tests and leukocyte migration inhibitory factor production reverted to baseline negative values when repeated 4 wk after discontinuation of therapy. After 4 additional wk on cimetidine, 4 of 4 patients showed strong positive skin tests and leukocyte migration inhibitory factor production to Candida antigen. Lymphocyte transformation was not affected by therapy.