Forty-three cases of isolated sphenoid sinus disease were reviewed. In 33 cases, headache was a presenting symptom. Seven of 29 cases of inflammatory disease and nine of 13 patients with tumors of the sinus presented with cranial nerve findings. When nonspecific visual disturbances were eliminated, two of 29 cases of inflammation and eight of 13 cases of tumors of the sphenoid sinus had cranial nerve deficits. Ten of 12 CT scans performed on patients with tumors of the sinus demonstrated bony erosion or perisinus extensions. This was not found in any of the 27 scans of patients with inflammatory disease. A thorough cranial nerve examination and a CT scan should be performed early in patients who present with vague and unusual headaches.