Our study of the molecular basis of SMA showed a frequency for SMN gene deletions in Macedonian patients of 77.0% (94.1% in type I, 87.5% in type II). Deletions involving both exons 7 and 8 (82.6%) was much more frequent than deletions of exon 7 only (17.4%). Our data support the hypothesis that the telomeric SMN gene may play a major role in determining the clinical severety of SMA [11-18,26-30]. Deletion of exon 5 of the NAIP gene was detected in 27.0% of SMA patients and in 6.7% par ents. A higher frequency of deletions in the NAIP gene was found in SMA type I (41.2%) than SMA type II (11.1%) patients. Deletion in exon 5 of NAIP, which is specific for the functional NAIP gene, shows wide frequency variation (0-67%) in different population studies [9-18]. The observation that deletions involving both SMN and NAIP genes are more frequently observed in SMA type I than SMA type II or SMA type III, suggests a correlation between the extent of the deletion and the severity of the phenotype. However, the fact that a great proportion of severely affected patients (41.2%) presented no deletions in the NAIP gene supports the hypothesis that in addition to the extent of the deletion, other factors may regulate the severity of the clinical course. A relationship between the number of gene copies and the disease pheno type has been suggested [19,20]. Deletions of one or both of exon 5 of the NAIP gene is not sufficient to cause the disease. Patients with no detectable deletion in exons 7 and 8 of the SMN gene could be due to deletions or point mutations in the promotor or in exons under investiga-tion or could not be identified under these analytical conditions.