Preterm neonates have an immature host defense that predisposes them to bacterial sepsis (Cairo AJDC 143:40, 1989). The risk of infection in LBWN ranges from 24.9-37.7% (avg. 31%) (Fanaroff NEJM 330:1107, 1994). In a Phase I trial, GM administered for 7 days to LBWN was well tolerated and enhanced myelopoiesis and PMN C3bi expression (CairoBlood 86:2509, 1995). We studied the feasibility and toxicity of 28 d GM in LBWN to prevent nosocomial infections. LBWN (n=61), BW 501-1000g,≤72 hrs of age, were randomized to receive GM (8 mcg/kg/d)IV over 2 hrs daily for 28 days or P. There was no difference in the P group vs GM group with respect to gestational age (26 vs 26 wks), weight (811±151 vs 776±168g, p=0.39), Apgar (4.7±2.3 vs 4.0±2.3), and CRIB score (6.4±4.7 vs 6.9±5.0). There was no significant difference in P vs. GM with respect to toxicity or complications including: RDS (43 vs 46%, p=0.948), BPD (71 vs 71%), days of mechanical ventilation (22±10 vs 22±10 d), inotropic support (2.2±3.9 vs 2.9±4.2 d, p=0.52), and total volume of RBC Tx (67±39 vs 65±34 cc). The ANC was increased in the GM vs P group at weeks 4 & 5 (14189 & 11540 vs 9306 & 5763/mm3). Eosinophilia was noted in weeks 1, 2, 3 in the GM group (p<0.02). The proportion of confirmed nosocomial infections of LBWN was significantly reduced in the GM vs P group (4/29 [14%] vs 11/31[35%], p=0.043). Positive cultures (some multiple) including sepsis, UTI, meningitis, catheter infections were also significantly fewer in the GM group vs P (5/29 [17%] vs 17/31 [55%], p<0.05): S. epidermidis (0 vs 4), S. aureus (1 vs 3), P. aeruginosa (0 vs 3), other bacteria (1 vs 4), fungal (3 vs 4). These results suggest that rhuGM-CSF beginning in the first 72 hrs of life is well tolerated in LBWN and may decrease the incidence of nosocomial infections. A larger randomized, double-blinded, placebo controlled Phase III trial is underway to confirm these initial findings. (Research grant support by Immunex Corporation)