Ecological and evolutionary theory predicts that genetic diversity of microparasites within infected hosts will influence the parasite replication rate, parasitemia, transmission strategy, and virulence. We manipulated clonal diversity (number of genotypes) of the malaria parasite, Plasmodium mexicanum, in its natural lizard host and measured important features of the infection dynamics, the first such study for any natural Plasmodium–host association. Hosts harboring either a single P. mexicanum clone or various combinations of clones (scored via three microsatellite markers) were established. Production of asexually replicating stages (meronts) and maximal meront parasitemia did not differ by clonal diversity, nor did timing of first production of transmission stages (gametocytes). However, mean rate of gametocyte increase and maximal gametocyte parasitemia were greater for hosts with mixed-clone infections. Characteristics of infections were more variable in hosts with mixed-clone infections than with single-clone infections except for first production of gametocytes. One or more of the parasite reproductive traits were extreme in 20 of 52 hosts with mixed-clone infections. This was not associated with specific clones, but diversity itself. The overall pattern from studies of clonal diversity for human, rodent, and now reptile malaria parasites confirms that the genetic diversity of infections in the vertebrate host is of central importance for the ecology of Plasmodium.