Ureaplasma urealyticum is a pathogen known to cause amnionitis and premature birth. Although controversial, it has been implicated as a cause of neonatal pneumonia as well as chronic lung disease. An inflammatory response has been demonstrated in the amnions of infected women and has been proposed for diseased newborns. Ureaplasma causes an increased release of IL-6 and IL-8, proteins associated with an inflammatory cascade. However, it has also been suggested that ureaplasma is a colonizing agent rather than a pathogen. We have previously shown that polymerase chain reaction (PCR) is a specific and sensitive method for detecting ureaplasma in endotracheal aspirates(Kuforiji, et al., Pediatric Research 39:297A, 1996). We sought to determine whether PCR (which should detect both pathogens and colonizing agents) correlated with a gross marker of inflammation, the WBC count. Between January 1994 and February 1996, we used the white blood cell (WBC) count as an inflammatory marker to compare differences between all PCR positive and PCR negative newborns. Fifty-three intubated newborns of less than 35 weeks, a mean gestational age of 28 weeks, and a mean weight of 1500 grams were studied by testing endotracheal aspirates by PCR and by examining serial WBC counts. Twenty-nine patients were positive for ureaplasma. WBC Count was higher in PCR positive than in PCR negative patients, F(1,13)=43.43, P<0.001, (MANOVA). The (mean ± SD) WBC count on day one was 13.90 ± 10.33 vs 9.47± 7.16, F(1,34)=6.09, P=.-10; on day two 14.67 ± 11.75 vs 10.55 ± 6.67, F(1,34)=4.06, P=.052; and on day fourteen 24.55± 13.21 vs 16.68 ± 7.88, F (1,34)=6.37, P=.016. Although WBC counts increased in both groups of patients, the response was greater in those positive for Ureaplasma. Conclusion: PCR is a sensitive tool for detection of ureaplasma and a positive test correlates with elevated WBC count in newborns suggesting that ureaplasma is a true pathogen in this population.