All neonates (n = 581) with birth weights less than 1501 gm admitted to seven neonatal intensive care units in Wisconsin and Iowa were candidates for a study aimed at the multivariate assessment of risk factors for chronic lung disease while controlling for baseline severity of respiratory disease. Data from 361 neonates were analyzed for all risk factors except fluids; only neonates weighing less than 1200 gm were included (n = 220). Information on traditional risk factors for chronic lung disease was abstracted. A total of 110 (30%) of the analyzed neonates were oxygen dependent on day 30 of life. The following baseline factors were associated with increased risk of oxygen dependence in a joint multivariate model: lower birth weight (odds ratio 1.4/100 gm), higher baseline severity score (odds ratio 2.7/doubling at 32 weeks gestational age), lower gestational age (odds ratio 2.4/week at severity 0), Apgar score at 1 minute (odds ratio 1.6/2 points), male gender (odds ratio 1.9), and nonblack race (odds ratio 2.2). After adjustment for all baseline factors, patent ductus arteriosus, ventilator pressure at 96 hours, oxygen at 96 hours, and fluid intake were associated with oxygen dependence. Neonates with a low baseline severity score who remained oxygen dependent had a higher intake of fluid relative to output, whereas neonates with a higher baseline severity score had higher fluid intake and output. Lack of weight loss was associated with increased severity but not with oxygen dependence. The results of this study generally confirm the significance of previously reported risk factors for chronic lung disease in a multivariate setting but show that risk factors may not have the same impact in neonates with different baseline severity.