Maternal infection during pregnancy may increase the risk of offspring neurodevelopmental disorders. The preclinical Polyinosinic-polycytidylic acid (PolyIC) model has become one of the most widely used approaches in maternal immune activation (MIA) research. However, variability in molecular weight may impact the immune activating potential of PolyIC. Nulliparous rats injected with high molecular weight PolyIC exhibit pronounced cytokine response and sickness behavior that was not observed in rats injected low molecular weight PolyIC. Although an essential next step is to extend these studies to pregnant animals, the preliminary results suggest that PolyIC molecular weight is an important experimental design consideration.