Previous studies have established a genetic component for susceptibility to malaria. Here we use a pedigree based approach, and transmission disequilibrium testing (TDT), to identify immune response genes that influence susceptibility to Plasmodium falciparum malarial phenotypes (parasite density and frequency of clinical episodes) in a Tanzanian population. Evidence for association was observed between markers in the TNF gene cluster and both the malarial phenotypes. There was weaker evidence for associations between HLA-DRB1*04, HLA-DRB1*10, and loci in the TCRBV region with parasite density. There was no evidence for association with polymorphisms in the IL10 promoter, IL1 gene cluster, or from the IL4/IL13 region.