Genetic polymorphism of the major glycoprotein (Gl) found in parotid saliva is determined by autosomal inheritance of one unexpressed and four expressed alleles. This hypothesis is supported by studies in 41 white families including 146 children. For 143 randomly collected salivas from whites and 82 randomly collected salivas from blacks, maximum likelihood estimates of the gene frequencies are as follows: for whites, Gl1 = 0.742, Gl2 = 0.040, Gl3 = 0.155, Gl4 = 0.017, Gl0 = 0.46; for blacks, Gl1 = 0.459, Gl2 = 0.050, Gl3 = 0.337, Gl4 = 0.044, Gl0 = 0.110. There is strong evidence for linkage of Gl/Pr (seven families, lod score at theta = 0 is 5.24) and G1/Db (eight families, lod score at theta = 0 is 4.45). The allelic products of Gl show evidence for linkage disequilibrium with the products of the Pr, Db, and Pa loci (P less than 0.0005). On the basis of varying degrees of linkage disequilibrium, Gl may be closer to Db than to Pr or Pa and on the "outside" of Db with respect to Pr or Pa. Amino acid analyses of Gl 1 and Gl 4 proteins show strong resemblances in composition to the major basic glycoprotein and the acidic proline-rich proteins of parotid saliva described by other workers. The polymorphic forms of the Gl proteins show microheterogeneity due to variability in charge and molecular weight. The electrophoretic polymorphism appears to be determined by apparent differences in molecular weights between the Gl proteins.