Fragile X (Fra-X) syndrome is the first cause of hereditary mental retardation (MR). Its incidence is 1/1000 males and 1/2500 females. Transmission is X-linked dominant. Males are more severely affected than females. Since 1989 we have used a clinical score with 16 features for the detection of affected males, which was validated with laboratory tests (SLAIP 1994). In this study we tested the effectiveness of this score for MR, modified for female population. It was applied to girls with cognitive deficit and/or MR. The score has 15 items, assigning 1 point to each one. (Familial history of male MR; height and cephalic circumference >p50; long ears; prominent ears; long face; high palate; hand's callus; hyperlaxity; depressed sternum; poor visual contact; hiperactivity; motor stereotipyes; self agression; language disorders and MR). Of 4084 patients with MR referred to the Department of Genetics during 6 years, 67 girls with MR without diagnosis were selected. (Microcephalics and MR with multiple malformations were excluded). Level of MR was measured as well as the presence of the fragile X site Xq27,3 (FUDR technique). Patients were divided in two groups. A) 16 girls(32.9%) Fra-X positive from 13 families. Mean age 9.25y. The score runned from 3 to 13 points (mean 8.19). Cognitive deficit was mostly border line and mild(75.1%). B) 51 girls (76.1%) Fra-X negatives, from 49 families. Mean age: 7.39y. The score runned from 2 to 8 (mean 4.16). MR was mostly mild and moderate (55.8%). The most consistent finding in the first group was positive familial history of affected males (93.3%). Since 1992 we were able to perform molecular studies to identify the mutation of the FMRI gene (Southern Bloth Technique) and we applied it to some patients of both two groups (15 from Fra-X+ group and 14 from the Fra-X-). Comparison of cytogenetic findings with the molecular studies showed that in the former sensitivity was 93,74% and specifity 100%. We conclude that this clinical score is not suitable for girls. The presence of cognitive deficit and familial history of affected males (93.8%) should serve as marker for performing cytogenetic and molecular studies, since women with the full mutation may not have other clinical features because of the Lyon phenomenon.