Sexual reproduction is an evolutionary ‘puzzle’. A sexual female ‘throws away’ half of her genes (during meiosis), and ‘fills up’ what she lost with genes from a male. Thus, sexual reproduction can only be successful if the offspring with the new mixture of genes should be more than twice as fit as if she had just made a copy of herself. A challenging hypothesis assumes that infectious diseases select for females that reshuffle the immune genes for their offspring in each generation. The required increase in quality could be achieved by females selectively ‘smelling out’ suitable immune-genes (i.e. Mhc alleles) in potential partners, which, in combination with the female's genes, offer optimal resistance against quickly changing infectious diseases. It was found that most three spined sticklebacks Gasterosteus aculeatus in natural populations around Plön, Germany, had intermediate instead of maximal numbers of different Mhc class IIB alleles. Furthermore, fish with an intermediate number of different Mhc alleles were infected with the lowest number of both parasite species and parasites per species. This suggests that Mhc heterozygosity was optimized instead of maximized. Can this immunogenetic optimum be achieved through female choice? In a flow channel design that allowed the detection of olfactory signals only, it was found that female three-spined sticklebacks that were ready to spawn preferred males as mates that in combination with their Mhc alleles would allow the production of offspring with the optimal number of Mhc alleles. Thus, mate choice in three-spined sticklebacks could have the two-fold advantage over asexual reproduction that is required to maintain sexual reproduction. The interaction of olfactory with visual signals in three-spined stickleback mate choice is discussed. The three-spined stickleback is a suitable model organism for studying the evolution of sexual reproduction in relation to optimizing offspring immune genetics although other fishes may be as suitable.