Glucose-6-phosphate dehydrogenase (G-6-PD) exhibits extensive heterogeneity in the Saudi population. The polymorphism of G-6-PD was investigated in different regions of Saudi Arabia, and G-6-PD variants were separated and identified on the basis of their electrophoretic mobility and activity towards glucose-6-phosphate. G-6-PD-B+ was found to be the most common phenotype, G-6-PD-A+ was found in each region but at a variable frequency ranging between 0.007 and 0.046. A second variant with normal activity but lower mobility than G-6-PD-B+ was identified among the Saudis at a frequency ranging from 0.000 to 0.028 in the different regions. In addition, a high frequency of variants with reduced activity was encountered in all regions. In males, a frequency of G-6-PD Mediterranean ranging from 0.046 to 0.261 was obtained, while G-6-PD-A* existed at a frequency ranging from 0.011 to 0.028. Furthermore, other variants with reduced activity but the same electrophoretic mobility as G-6-PD-B+ were detected at a high frequency among the Saudis.