In a prospective study elastase alpha 1-proteinase inhibitor (E alpha 1PI), polymorphonuclear (PMN) count, the immature to total neutrophil count ratio (I/T ratio), and C-reactive protein (CRP) were analysed in 74 patients (76 cases) with neonatal septicaemia at the time of initial clinical symptoms. At that early stage of the disease, 94% of the patients had abnormal values for E alpha 1PI, 71% for I/T ratio, 61% for PMN count, and only 54% for CRP. PMN count was a poor indicator of septicaemia. Neutropenia, present in 26% of all patients, was related to normal E alpha 1PI in only 4 patients. The combined use of E alpha 1 and I/T ratio was the most sensitive indicator. In all patients irrespective of causative bacteria or disease onset at least one of these parameters was elevated. In early-onset septicaemia (n = 31), normal CRP values occurred significantly more often (63%) than in late-onset sepsis (33%). Even in five of the seven fatal cases, initial CRP measurements were normal. The sensitivity of PMN count and I/T ratio did not differ significantly between early- and late-onset septicaemia. Laboratory changes observed in 18 newborns during the first 3 days of the septic episode show that the rate of pathological values for E alpha 1PI and I/T ratio was highest at the time of initial clinical symptoms and decreased on days 2 and 3. In contrast, CRP reached maximal values as late as day 2 (88% abnormal values), followed by a decrease on day 3. We conclude that the use of E alpha 1PI may improve the laboratory detection of neonatal septicaemia especially if used in combination with I/T ratio.