The pathogenesis of the periventricular intraparenchymal echodense lesion (IPE) observed in association with germinal matrix-intraventricular hemorrhage (GM-IVH) in premature neonates is unclear. The objectives of this study were to determine (1) the temporal characteristics of GM-IVH and IPE, (2) the basic characteristics of the IPE, and (3) the relationship of clinical events, including surfactant administration, to IPE. One hundred twenty-four neonates of less than 1250 g birth weight were prospectively evaluated. IPE was defined as an echodensity greater than 1 cm in diameter by cranial sonography. Fifteen (12%) neonates developed IPE in association with GM-IVH (group 1); 33 neonates developed GM-IVH only (group 2) and 76 neonates without GM-IVH served as comparison group (group 3). IPE was essentially an asymmetrical lesion; both sides of cerebrum were equally affected. The lesion was diffuse in 9 neonates and focal in 5. IPE occurred both early, at 36 hours or before (n = 8), and later, ie, between 48 and 96 hours (n = 6). In one neonate IPE was diagnosed at autopsy. GM-IVH and IPE were noted simultaneously in neonate with the earlier onset IPE (diagnosed within 36 hours); GM-IVH preceded the IPE by 6 to 48 hours when the lesion was of a later onset. Surfactant was administered to 13 (87%) group 1, 24 (73%) group 2, and 35 (46%) group 3 neonates. Pulmonary hemorrhage developed in 9 (60%) of group 1, 3 (9%) group 2, and no group 3 neonates. Symptomatic patent ductus arteriosus occurred in 12 (75%) group 1, 15 (45%) group 2, and 15 (20%) group 3 neonates. The onset of symptoms associated with patent ductus arteriosus was earlier in group 1 vs group 2 or group 3 neonates, ie, 70 vs 172 hours. Nine (60%) group 1 neonates, 6 (18%) group 2, and 5 (7%) group 3 neonates died. The cranial sonogram was markedly abnormal in all 6 group 1 survivors. Stepwise polytomous logistic regression indicated that birth weight, gestational age, and emergent cesarean section were the best predictors of GM-IVH + IPE.(ABSTRACT TRUNCATED AT 250 WORDS)