In 1987 we described a unique syndrome of periodic episodes of fever frequently accompanied by aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) (Marshall et al J Ped 1987;110:43-46). Laboratory studies are normal except that the white blood count and the erythrocyte sedimentation rate are frequently elevated during episodes. A questionnaire describing demographic and clinical characteristics was completed by the families of patients suspected to have the syndrome. Using this information we have identified 96 children from 22 states and 3 foreign countries with the syndrome. The mean age at onset was 2.8 years (range 0.7-11yrs). There were 43 females and 53 males. Episodes occurred every 28 ± 10.7days and lasted 4.8 ± 1.4 days. Maximal temperatures were typically >104°F. The average number of episodes per year was 11.4. In only one case was there a possible family history of periodic fever. Antibiotics did not influence the course of episodes. Parents of 84 children were interviewed by telephone and submitted copies of medical records. Mean follow-up for patients was 3.3 years(Range 0.1-9.4). Fevers had completely resolved in 45 (54%) after a mean of 4.2 years. Of 36 continuing to have periodic fevers, 19 had persisted for more than 5 years. No patient had developed autoimmune or malignant disease. Neurologic disorders had been diagnosed in 3 patients: autism in one, attention deficit disorder (ADD) in one, and ADD, Tourette's syndrome, and obsessive compulsive disorder in the third. Several different treatments were attempted. Parents reported that prednisone promptly aborted the attacks in 37/49 (76%) and ibuprofen alleviated the symptoms during attacks in 23/69(33%). Cimetidine and tonsillectomy were reported to prevent attacks in 8/28(29%) and 7/11 (64%), respectively. PFAPA is easily diagnosed because of the periodicity of febrile episodes and the consistency of associated symptoms. It is much more common than cyclic neutropenia which it closely resembles with respect to periodicity and symptoms. Extensive laboratory investigations are unnecessary in most cases. The disorder appears to resolve in most patients and is not associated with the development of severe sequelae.