Hb City of Hope [beta 69(E13)Gly----Ser] was detected by reversed phase high performance liquid chromatography in an asymptomatic carrier from Naples, Southern Italy. The amino acid substitution, identified by fast atom bombardment mass spectrometry, was due to a TGG----TGA substitution as assessed by DNA sequencing. Analysis of the chromosomal background indicates that the globin gene cluster containing the mutant gene has most probably been rearranged by a recombination event, since the mutation was associated with restriction fragment length polymorphism haplotype IX, instead of haplotype I, as previously reported.