We have searched for a possible association of the genetic polymorphism of Phosphoglucomutase locus 1 (PGM1), a key enzyme in carbohydrate metabolism, with body mass.Adults (n = 257) with type 2 diabetes, 74 children referred for "obesity," and 740 consecutive healthy newborn infants were studied. Body mass index, body weight, birth weight, and PGM1 phenotype were determined. Sexes were analyzed separately.In type 2 diabetes, females carrying the PGM1*2 allele are less represented among subjects with extreme body mass index deviation as compared with other classes of subjects. Among children referred for "obesity," females carrying the PGM1*2 allele are less represented among children with extreme body weight deviation. Among consecutive infants, in both sexes the proportion of those showing a birth weight higher than the 3rd quartile is lower in homozygous PGM12/2 subjects than in other PGM1 phenotypes.The data suggest that during extrauterine life, females carrying the PGM1*2 allele are relatively protected from extreme body mass increase. During intrauterine life, PGM12/2 homozygotes show a tendency to low body mass increase. Because PGM1 enzymatic activity depends on its phosphorylation status by the kinase Pak1, both structural differences of the PGM1 allelic product and different rates of activation by Pak between sexes might be responsible for the pattern observed. At present, the effect of other genes near PGM1 and in linkage disequilibrium with it cannot be ruled out.