To better define the need for antibiotic therapy, several tests recommended as helpful in diagnosing neonatal sepsis were evaluated in 376 neonates during the first week after birth. The five most useful tests (with definitions of abnormality) were: band/total neutrophils (greater than or equal to 0.2); leukocyte count (less than 5,000/cu mm); latex-C-reactive protein (positive greater than 0.8 mg/100 ml); ESR (greater than or equal to 15 mm for the first hour); and latex haptoglobin (positive greater than 25 mg/100 ml). When these five tests were applied early (at the time infection was suspected and blood culture sent), 28 of 30 cases (93%) subsequently proven to have infection had two or more abnormal tests. This compares with only 24 of 320 babies (8%) with no subsequently documented evidence of infection. Of all babies who had two or more tests positive (n = 71), 39% had proven sepsis, and an additional 23% had "very probable" infection. The combination of leukopenia and an elevated band/total neutrophil ratio seems to be particularly predictive of sepsis (13 of 17 babies with this combination had proven sepsis). When less than two tests were positive, the probability that sepsis was not present was 99%. These simple, rapid tests require no special laboratory facilities and provide a valuable adjunct in the early detection of the neonate with sepsis.