We questioned whether the evidence for the genetic component in Parkinson's disease (PD) in Caucasians could be explained by the causative and susceptibility genes that have already been identified. We estimated heritability of risk and age at onset of PD in a well-characterized sample of 504 nuclear families (2828 individuals). After excluding families with known pathogenic mutations and accounting for the major susceptibility genes, the heritability of risk of developing PD was 0.41 (P=0.01). These data suggest that approximately 40% of the variation in susceptibility to PD is due to as-yet unidentified genes, the remainder is likely environmental.