SUMMARYCommon variable immunodeficiency (CVI) is a heterogeneous condition characterized by arrest in B cell differentiation, A high frequency of null alleles ofthe C4 gene has been reported in patients with this disorder. We investigated the restriction fragment length polymorphisms (RFLP) ofthe MHC class II genes HLA-DRB, DQA, and DQB, the class III gene C4 and the tumour necrosis factoralpha (TNF-a) gene in 40 Caucasian patients. The results showed an increase in HLA-DR3 in patients (40% vs 30-5%), but, more significantly, there was a striking increase in the number of CVI patients who carried a deletion ofthe C4A gene (46% vs 25%), In both patients and controls there was strong allelic association between HLA-DR3 and C4A deletion, and HLA-DR3 and TNF-a, Our results suggest that genes present on an extended haplotype containing these three polymorphisms contribute to genetic susceptibility to CVI,