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Cyclic seasonal variation of genotype-specific fertility could interact with endemic diseases characterized by seasonal variation of severity resulting in changes of gene frequencies in the course of generations. Assuming that a given allele A has a frequency PI\' in infants conceived in the cold season and a frequency of Ps in those conceived in the warm season and assuming that general fertility is the same in the two seasonal periods, the gene frequency in the population is Pm = (Pw + Ps)/2; this frequency remains constant over the course of generations. The introduction of an endemic disease bearing negatively on general fertility and characterized by a seasonal pattern of severity could result in variations of the A allele frequency. If the maximum of endemicity coincides with the maximum value of the allele A frequency, the frequency of allele A will progressively decrease. A simple mathematical algorithm has been applied to two polymorphic enzymes (ACPI and G6PD) correlated with past malarial morbidity in Sardinia and the Po River delta. The two systems show differences in gene frequency in relation to season of conception. The theoretical changes fit quite wen with the data observed in Sardinian and Po delta populations, thus suggesting a mechanism that is an alternative to or concurrent with the classical mechanism that assumes a direct connection between the genetic systems and the biology of the malarial parasite.