Thrombocytopenia occurs frequently in newborn infants with sepsis, but the exact mechanism remains obscure in those infants who do not have evidence of disseminated intravascular coagulation. Since recent work has suggested a possible immune mechanism for thrombocytopenia observed in adults with sepsis, we have investigated the role of platelet-associated immunoglobulin in severe neonatal infections. To detect PAIgG we use a method employing protein A and peroxidase-antiperoxidase as a labeled antibody. PAIgG was quantitated by phase contrast microscopy and expressed as a reactive index. Our control group included 16 normal newborn infants whose mean RI was 0.65±0.01 SE. In addition to the control group, five infants with nonimmune thrombocytopenia were included; their mean RI was 0.66±0.01 SE. Seventeen newborn infants with severe infections were assayed for PAIgG. Eight of nine infants with bacterial infections had increased RI, with a mean of 1.16±0.03 SE (P<0.01). Six of the eight infants with viral infections had elevated RI, with a mean of 1.23±0.03 SE (P<0.01). These findings suggest that an immune mechanism may be involved in the thrombocytopenia of severe neonatal infection.