Objective: To explore the association of neonatal interferons (IFNs) with spastic cerebral palsy (CP) and with other measured substances. Study design: Assays of archived neonatal blood of 31 predominantly term children with CP and 65 children in a control group were obtained by recycling immunoaffinity chromatography with laser-enhanced fluorescence and chemiluminescence detection. Results: Fourteen of 31 children with spastic CP had concentrations of IFNs-⍺, β, and γ exceeding any control. Levels of interleukins-1, 6, 8, tumor necrosis factor-⍺, chemokines, colony stimulating factors, transforming growth factor-β, complement components and regulators, certain neuropeptides, and thyroid hormones also differed from control levels in these 14 children. The 17 children with CP whose IFN concentrations were within the control range had levels of inflammatory cytokines higher than but near to control values; 13 of these 17 had values for coagulation factors that exceeded control values. Seven of 9 children with spastic diplegia had high IFNs, and 8 of 10 hemiplegic children had normal IFNs. Conclusion: Neonatal IFNs exceeding control concentrations were associated with other biochemical and clinical indicators of inflammation and with spastic diplegia. In these children with CP, IFNs within the control range were associated with concentrations of other inflammatory markers that were near to control values and with spastic hemiplegia. (J Pediatr 1999;134:324-32)