The clinical course of patients with signs and symptoms suggestive of temporal arteritis but with negative temporal artery biopsy specimens was evaluated. Ninety-one patients undergoing a biopsy formed the basis of this study. Of these, 63 patients had no evidence of arteritis on biopsy, and 28 patients had biopsy specimens showing granulomatous inflammation. False-negative findings from biopsy specimens occurred in 5% of patients who had the disease. Cancer was the final diagnosis in 21% of patients with negative biopsy specimens v 3% of patients with temporal arteritis. Various chronic systemic inflammatory diseases were found in 16% of patients with negative biopsy specimens, while none of the patients with temporal arteritis had additional systemic inflammatory diseases. Patients with proven arteritis were notably older and had higher ESRs than patients without the disease. However, no laboratory test or frequently observed symptom or sign noted on initial examination, considered alone or in combination with other findings, had diagnostic sensitivity or specificity as high as temporal artery biopsy.