Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = .001 for each additional kilogram). Maternal pre-eclampsia/eclampsia was significantly associated with greater odds of ASD (OR = 1.85, p < .0001 without controlling for birth weight; OR = 1.69, p = .0005, when controlling for birth weight). We conclude that reduced birth weight partially mediates the association between pre-eclampsia/eclampsia and ASD. Additional research is needed to investigate the potential mechanism(s) by which pre-eclampsia/eclampsia may influence ASD risk.