The family of two siblings with severe hereditary spherocytosis was investigated. The decrease was evident on both the α‐ and the β‐chains. The parents were haematologically normal. The mother was heterozygous for the low‐expression polymorphic allele α^LEPRA. The father was heterozygous for a novel combination in which one allele showed the α‐spectrin low expression polymorphic alleleα^LELY, while his other allele showed the α^LELY polymorphism in cis with a G→A substitution, named Bicêtre, found at the extreme 3′ end of exon 51. This combination was designated . The children were compound heterozygotes for alleles α^LEPRA and . Reverse transcription polymerase chain reaction detected only trace amounts of the mRNA coding for . Mutation is therefore an essentially null mutation with no functional protein product. The lack of disease in the α^LELY/ father compared with the marked haemolysis in the α^LEPRA/ children showed that expression of allele α^LELY is not low enough to expose null α‐spectrin alleles on the other chromosome. Quantitative estimations from these findings suggest that, to evoke spherocytosis, it is necessary that α‐spectrin expression must be reduced to less than 25% of normal, while a reduction to 8% is sufficient.