Malaria parasites are highly diverse organisms, in which multiple-species infections are quite common. For example, in Papua New Guinea there are reports of people simultaneously infected with the four species of human malaria (P. falciparum, P. malariae, P. ovale and P. vivax). Many field samples of rodent malaria parasite contain multiple parasite species. Indeed P. vinckei co-infecting with P. chabaudi was so common that they were thought to be a single species for over a decade.

Co-infecting species of malaria parasites (in both rodent and human hosts) can, to some extent, be viewed as using different habitats in their hosts as they preferentially infect red blood cells of different ages. For example, of the rodent malarias, P. berghei and P. yoelli preferentially infect immature red cells, P. vinckei has a strong mature cell preference and P. chabaudi shows no significant preference. However, gametocytes from all co-infecting species are likely to find themselves in the same mosquito blood meals so speciation may be sympatric rather than allopatric.

The vectors for some of the rodent malarias are not yet known but given that gametogenesis and mating in co-infecting species are stimulated by the same cues, it seems likely that there is potential for hybridization, as gametes of multiple species will be searching for mates within the same restricted time and space window. However, conventional wisdom states that hybrids do not form but we don't know what factors prevent hybridisation between co-infecting species.

In most taxa, males are not 'sperm-limited' so fertilising the 'wrong type of female' doesn't incur significant fitness costs as only a small proportion of a male's gametes are wasted. However, male malaria parasites are rarely able to make as many as eight gametes so we expect strong selection against 'wasting' them on hybrid fertilizations if viable offspring are not formed. Given this novel mating biology and consequent strong selection to maximise successful matings, we might expect that pre-zygotic hybridisation barriers occur. For example, there may be species-specific receptors for male and female gamete fusion or males may be preferentially attracted to con-specific females. Pre-zygotic barriers could also explain instances where fewer wild caught mosquitoes contain mixed species infections than expected by the prevalence of mixed infections in humans.

The mating behaviour of malaria parasites can now be investigated thanks to the availability of rodent malaria parasites that have been genetically modified to express fluorescent proteins or be defective in the fertility of males or females.