Previous studies have indicated that tumor necrosis factor-alpha (TNF-alpha) may play a pathophysiologic role in experimental sepsis by group B streptococci (GBS). We tested the efficacy of some TNF-alpha and eicosanoid inhibitors in a neonatal rat model of GBS disease. The drugs tested included cloricromene, SKF86002, pentoxifylline, CGS8515, ibuprofen and LY203647. None of these compounds were protective against GBS infection, with the exception of pentoxifylline, that produced a moderate enhancement of survival time. Further studies are needed to ascertain if specific inhibitors of TNF-alpha, alone or in conjunction with antibiotics, may be effective as therapeutic agents in neonatal GBS sepsis.