Neonates with hyperbilirubinemia commonly undergo a battery of laboratory tests. We used a computerized database and medical records to study the frequency, cost, and yield of these tests in 2443 infants born at the University of California, San Francisco, between 1980 and 1982. Four hundred forty-seven (18%) of the infants met standard criteria for "nonphysiologic" hyperbilirubinemia; the incidence varied from 9% in blacks to 31% in Asian infants. About 55% of these 447 infants received a $125 "hyperbilirubinemia workup." Hospital discharge diagnoses on all 447 hyperbilirubinemic infants were reviewed. In 214 (48%), no cause of the jaundice was identified. An additional 145 (32%) had a possible cause apparent from history, physical examination, or initial hematocrit determination. The only diagnosis made as a result of routine investigations of hyperbilirubinemia was possible ABO or Rh isoimmunization in 75 infants (17%). Nonphysiologic hyperbilirubinemia may be more common than previously reported. The recommended tests are expensive and rarely lead to diagnoses other than ABO or Rh isoimmunization. Their routine use should be reevaluated.