Tumour necrosis factor-alpha (TNF-alpha) is an important mediator in the pathogenesis of Gram-negative shock. In order to assess the role of TNF-alpha as a marker of the severity of infections in the neonates, serum TNF-alpha concentrations were determined at the time of septic work-up in 69 newborns (gestational age: 28-40 weeks). Nine patients had systemic infection (group A), four of them with signs of circulatory failure. Eleven patients had positive cultures of gastric aspiration or placental smears (group B) and 49 patients had completely negative septic work-up. Patients of group A had significantly more elevated serum TNF-alpha levels than patients of group B and C. Within group A, patients with circulatory failure had mean serum TNF-alpha concentration of 2165 +/- 817 pg/ml versus 27 +/- 8 pg/ml in newborns without shock. Serum TNF-alpha concentrations of more than 15 pg/ml detected systemic infections in eight out of nine patients. The specificity was 98% (1 elevated TNF-alpha concentration out of 60 non infected patients). These data indicate that premature neonates and term newborns are able to produce TNF-alpha when they are infected. Highly elevated TNF-alpha concentrations are found in severe systemic infections causing cardiovascular impairment.