To evaluate the clinical characteristics of transient hyper-phosphatasemia of infancy (THI), a syndrome of marked benign transient increase of serum alkaline phosphatase (SAP), we retrospectively studied eight patients with the following: 1) SAP > 3x upper limits of normal, 2) no hepatobiliary, metabolic, neoplastic, or osseous abnormality, 3) SAP level returning to normal without therapy. Mean age was 9.5 months, range 3-14 months; five patients were female. Mean maximum SAP was 2,460 IU/dl, range 1115-7276 IU/dl; mean time for SAP to normalize was 4.6 weeks (range 1.5 - 8 weeks); six patients (63%) had gastrointestinal symptoms (gastroesophageal reflux, food allergy, chronic diarrhea). One patient was < 5th percentile for weight. Serum calcium, phosphorus, transaminases, and bilirubin were normal. Skeletal radiographs and bone scans were normal. We conclude: 1) in infants, extreme elevations of SAP are often benign; 2) a minimal workup should include skeletal radiographs and liver function studies; 3) SAP should be repeated biweekly, and if decreasing extensive studies should not be performed. Because of high incidence of gastrointestinal (GI) symptoms we speculate that THI may be secondary to an acute GI injury with transmucosal passage of liberated intestinal alkaline phosphatase.