Loss of heterozygosity (LOH) affecting loci at 11p13 and 11p15 occurs in childhood and adult carcinomas, including non-small cell lung cancer (NSCLC). In NSCLC, the highest reported frequency of LOH was 72% at the 11p13 catalase (CAT) locus. As this locus is centromeric to the Wilms' tumour (WT1) locus, possible involvement of WT1 in the pathogenesis of NSCLC was considered. We thus examined 101 cases of NSCLC for LOH at the WT1 and five other polymorphic loci along 11p. At 11p13, the frequencies of LOH were 20% (9/46) at the FSHB locus, 9% (5/53) at the WT1 locus, and 15% (6/41) at the CAT locus. The shortest region of overlap (SRO) at 11p13 was mapped centromeric to, but excluding, the WT1 locus. Only adenocarcinomas showed LOH in this region. At 11p15, LOH affected 23% (18/77) of informative cases, with the highest frequency of 36% at the insulin (INS) locus. The SRO at 11p15 was mapped telomeric to the RRM1 locus. A third region, at 11p13-15 between WT1 and RRM1, was also affected by LOH. LOH at 11p correlated significantly with advanced T stage and nodal involvement in NSCLC tumours. In the squamous cell carcinoma subtype, LOH along 11p also correlated with nodal involvement. Furthermore, squamous tumours with LOH involving 11p13 loci had significantly worse survival than those without LOH. These data suggest that tumor suppressor gene(s) on 11p affect the progression of NSCLC, particularly squamous cell carcinomas.