A survey of limb girdle muscular dystrophy has been carried out in 1995-1996 in the Basque province of Guipuzcoa (702@000 inhabitants). Patients were ascertained through medical records kept by local hospitals and through information held by patients support groups. The diagnostic criteria were those agreed tt the ENMC workshop held in Naarden in 1995. All patients were re-examined by two neurologists and underwent electrophysiological and immunohistochemical studies whenever necessary. Serum CK, bidimensional echocardiography and respiratory evaluation were also performed in order to investigate more deeply phenotypic variations. Genetic studies were carried out at Genethon and were designed to demonstrate a possible linkage to chromosome 15 (LGMD2A locus) or to test known mutations. A primary screening enabled to select 62 patients out of which 8 turned out to have an alternative diagnosis (2 with Becker muscular dystrophy, 3 with SMA, 1 with myotonic dystrophy, 1 with α-sarcoglycanopathy, 1 with an undetermined myopathy), and 4 were not available for the study. For the remaining 51 patients (29 men, 22 women, mean age 38.9 years ± 14.24), the clinical presentation was consistent with previous descriptions of LGMD in patients reported by M. Fardeau in the Reunion. A molecular screening for CANP3 revealed that 29 families corresponding to 38 patients were harbouring a mutation in the calpain gene while the status of the 13 other patients is pending. Interestingly, 18 families were homozygous for a mutation in exon 22 whereas 8 families were heterozygous for exon 22 and 1 family was homozygous for exon 21. The prevalence rate of LGMD 2A found in this Basque population (68100 000) is one the highest so far reported world-wide. This cluster of patients, mostly of Basque origin, is presumably due to socioeconomical (inbreeding, no admixture with neighbouring Spanish people) and geographical (landlocked mountainous valleys) factors. The existence of one main mutation in exon 22 suggest a founder effect. Correlations between genotype and phenotype are still under way and demonstrates some similarities in the exon 22 mutation carriers and some discrepancies for the others.