Objective: To investigate the cooperative interaction among five genetic systems (phosphoglucomutase locus 1, adenosine deaminase locus 1, acid phosphatase locus 1, adenylate kinase locus 1, and haptoglobin) concing their effects on natural fertility in humans. Natural fertility has been evaluated by a model of age related differences between the distributions of types among pregnant women. Methods: A total of 137 nonsmoking consecutive puerperaes from the white population who had delivered their first b baby in the Matity Department of S. Massimo Hospital of Penne were studied. The phenotypes of the five systems studied were determined by starch gel electrophoresis. Statistical analysis was performed using the statistical package for the social science. Results: There was a highly significant negative correlation between matal age and the number of genetic factors showing a lower matal age at the birth of the first child, which suggested a positive cooperative interaction among these factors concing their effects on fertility. Conclusions:In the relationship of mother-fetus, besides nutritional factors, genetic factors involved in immunological interaction of the embryo with the mother are of paramount importance. Haptoglobin and adenosine deaminase locus 1 polymorphisms are involved in immune reactions and our data indicate that genetic variability within these systems gives a more important contribution to variation of human fertility as compared to acid phosphatase locus 1, phosphoglucomutase locus 1 and adenylate kinase locus 1 that are mainly involved in metabolic functions.