A review was conducted to determine the trends in exchange transfusion (ET) of newborn infants at the Yodogawa Christian Hospital during the past 18 years. At that hospital in 1957, the first ET was performed on a term infant with severe hemolytic jaundice caused by rhesus factor (Rh) incompatibility. By 1989, ET had been performed in more than 1400 newborn infants. These cases of newborns who had had ET were retrospectively reviewed, with a focus on every 3 year period from 1974 to 1992. The total number of infants requiring ET noticeably decreased from 68 cases (14.0% of total admissions) in 1974 to 19 cases (6.1% of total admissions) in 1992. (chi 2, P < 0.001) There were three major significant changes in ET during those years. The first was a change in the subjects for ET. The incidence of ET for term infants showed a marked decrease, while the incidence of ET for preterm infants, especially for very low birthweight (VLBW) infants (< 1500 g), noticeably increased. The second was a change in indications for ET. There was a marked decrease in the need for ET as a result of hyperbilirubinemia, while the incidence of ET because of other etiologies, such as septicemia and/or disseminated intravascular coagulopathy, noticeably increased. The third was a change in the technical methods of ET. Now at the Yodogawa Christian Hospital, 100% of the infants are given ET with an automated peripheral two-site method, instead of the Diamond method. Although ET might still be a useful treatment for severe hyperbilirubinemia and other acute problems, the total number of ET noticeably decreased in accord with a decrease in the number of severe hyperbilirubinemia in term newborns. On the other hand, the incidence of ET in preterm infants increased relatively, accompanied by an increase in the survival of VLBW infants. The automated two-site method is the preferred technique for ET at the Yodogawa Christian Hospital, rather than the Diamond method. Further changes in ET might occur in accord with new alternative measures in future.