Thirty-three prospectively studied neonates born to mothers using methadone plus other drugs developed significant thrombocytosis by the second week of life compared to platelet counts performed during the first week. This increase persisted for over 16 weeks, with a further short-lived significant peak at 10 weeks of age. Platelet counts exceeding 1,000,000/mm3 were found in seven infants. Thrombocytosis was not related to withdrawal symptoms or treatment (phenobarbital or paregoric). No thrombocytosis was found in 36 normal control infants up to eight weeks of life. Twenty-eight of the study group infants were evaluated for circulating platelet aggregates. Thirteen patients had a normal aggregate index and a mean platelet count of 468,000/mm3; 15 patients had increased aggregates and mean platelet count of 754,000/mm3. The risk for increased circulating platelet aggregates correlated directly with an increase in platelet count. Thrombocytosis and increased circulating platelet aggregates may be factors in the pathogenesis of the focal infarcts, and subarachnoid and germinal plate hemorrhages, described at autopsy in infants of addicted mothers.