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The entomopathogenic fungus Metarhizium anisopliae var anisopliae produces a family of cyclic peptide toxins, destruxins (DTX), both in culture and in vivo in mycosed insects. The contribution of these insecticidal toxins to the disease process has been investigated in the tobacco hornworm, Manduca sexta (Lepidoptera), the desert locust, Schistocerca gregaria (Orthoptera), and the vine weevil, Orthoptera sulcatus (Coleoptera), A significant negative correlation was found between the titer of DTX production in vitro of isolates of M. anisopliae var anisopliae pathogenic for Otiorhynchus and the median lethal time, suggesting a role for the toxin in isolate virulence. The same was true for Manduca-active isolates. A key exception was isolate 703, This is highly virulent for M. sexta, yet does not produce DTX in vitro, grows largely as hyphal fragments in the hemolymph of infected insects, and does not cause host paralysis. These results are discussed in the light of the hypothesis that there are at least two possible virulence strategies among isolates of M. anisopliae var anisopliae pathogenic for Manduca viz the "toxin strategy" and the "growth strategy." For locusts, a strong positive correlation was found only between in vitro toxin production and percentage mortality of individuals in which sporulation did not occur on the cadaver. To account for this, it is suggested that if DTX kills locusts before the fungus has established itself, then the pathogen may not compete effectively with the saprophytic flora and, as a result, fails to sporulate. It is concluded that, in the pathogenesis of M. anisopliae var anisopliae for all three insects, there is a relationship between the titer of DTX production of isolates in vitro and the killing power. (C) 1999 Academic Press.