Defective steroid synthesis due to derangements of 21-hydroxylase gene (CYP21) constitutes the most frequent cause of congenital adrenal hyperplasia (CAH) and is one of the most frequent inborn errors of metabolism. The defect is inherited as an autosomal recessive disorder that affects 1 in 13000 live births worldwide. The genetics of CYP21 are unusual and complicated. Random deletions and de novo mutations almost never occur, instead, during meiosis gene conversion occur which transfers deletrious point mutations from the inactive (CYP21P) to the corresponding sequence of the active (CYP21) causing either complete or partial inactivation of 21-hydroxylase activity. ASPCR was used for the detection of 4 of the most common point mutations inCYP21 gene ( I 2 splice mutation, 8bp deldtion in exon 3, I172N mutation in exon 4, V281L mutation in exon 7).In 11 salt wasting Egyption infants. For each mutation site in question, two PCR reactions were performed .One reaction detected the normal allele, the other detected the mutant .Each reaction contained either a normal or mutant primer in conjunction with a common primer. In I2G mutation a third reaction containing the C variant was carried out. The normal and mutant primer differ by 3' terminal nucleotide that coincide with the site of the possible point mutation. Homozygous alleles show a PCR product only in the reactions of either normal or mutant primers. If the sample was heterozygous , a PCR product was generated from both the normal and the mutant reactions. In the 22 alleles ,examined, 2alleles were carrying 8bp deletion, 3 were carrying I2G mutation,4 with I172N,4 with V281L and in 11 alleles none of the 4 point mutations examined could be detected. The wide range of CAH phenotype is associated with multiple mutations known to affect CYP21 gene. The phenotypes are not always correlating with allelic variations in the CYP gene. A strict and long term clinical observation is still mandatory in all patients with CAH even after hormonal and molecular diagnosis. In conclusion, the wide range of genetic mutations reported for CYP21 gene calls for more extensive molecular work. This is the first step in establishing a battery of common mutations in Egyptian children, which will ultimately be adapted in prenatal screening for CAH.