Several immune abnormalities have been noted in autistic subjects. These associations have been extended to the Major Histocompatibility Complex (MHC), a section of DNA remarkable for the number of encoded proteins with immunological functions. The strongest MHC association identified thus far is for the null allele of C4B in the class III region. The complex allelic composition of C4 as determined by immunoelectrophoresis is discussed. Low levels of C4 resulting from the null allele may be important in disease pathogenesis especially since C4 has been identified in developing brain neurons. The DNA region just telomeric to C4 has several genes including tumor necrosis factor which encode proteins with immunological functions. These proteins may act in concert with C4 in disease contribution and the genes should be more closely examined.