Two patients with Cronkhite-Canada syndrome (CCS) are reported, both of whom had diffuse alopecia, nail and skin changes, gastrointestinal polyposis, diarrhea, and wasting. A scalp biopsy was performed in one patient, and the specimen showed a marked noninflammatory loss of follicular units, miniaturization of the hair shafts, markedly dilated follicles, and a heavy deposition of glycosaminoglycans in the reticular dermis. This patient responded to prednisone therapy. The other patient was found to have elevated gastric acid levels and responded to ranitidine therapy. The conditions of both patients are now in remission two and six years later, respectively. Our patients have shown a temporally related remission of disease during treatment with prednisone and ranitidine, suggesting that each agent may be effective in CCS. However, randomized placebo-controlled trials are needed to prove the efficacy of these therapies. Further investigation of the histopathologic features of the associated alopecia may determine its cause.