PURPOSE: Theophylline, an adenosine antagonist commonly used in premature infants to treat apnea, has been shown to decrease erythropoietin levels in adults. We studied the effect of theophylline on serum erythropoietin levels in premature infants with apnea. METHODS: Subject were 12 premature infants with apnea who were admitted to the NICU, Chosun University Hospital. The first dose of theophylline was 5mg/kg, given intravenously, followed by 1 to 2mg/kg per day. Serum levels were maintained between 5 and 12microgram/dl with dosage adjustments. Erythropoietin, hemoglobin, hematocrit, reticulocyte count, erythrocyte indices were obtained on the last day of theophylline treatment and again 1 week later. Erythropoietin levels were determined by radioimmunoassay. Blood transfusions were avoided a week before and during the study period. RESULTS: 1) Hemoglobin and hematocrit levels were decreased at 1 week after the discontinuation of theophylline treatment compared to the last day of theophylline treatment (P<0.05), but reticulocyte count (%) was increased (P<0.05). 2) There was a significant increase in serum erythropoietin levels from 3.31+/-1.53u/l to 6.68+/-2.41u/l (P<0.05). 3) No correlation was found between erythropoietin levels and the number of days on respirator, the number of days of O2 supply, the number of apneic episodes, the number of blood transfusion, the period of theophylline treatment and the theophylline blood levels. CONCLUSIONS: We suggest that prolonged treatment with theophylline might reduce erythropoietin production in premature infants.