To evaluate the hypothesis that mucin gene VNTR polymorphisms are associated with severity of CF lung disease, we used HinfI-digested DNA and Southern blot to determine the VNTR allele length polymorphisms for MUC1, MUC2, and MUC5AC, and used PCR methods for MUC7. Southern blot experiments were carefully optimized to maximize the reliability of allele size calls, using a mixture of samples from patients with “severe” and “mild” lung disease on each gel, standard internal markers and size standards, and a genetically homogenous CF population (Caucasian Phe508del homozygotes). Here, MUC2 is linked to cystic fibrosis.