Ribosomes in lysates prepared from the mycelia of Aspergillus giganteus MDH 18894, which are actively secreting alpha-sarcin, do not contain the alpha-sarcin lesion. However, the addition of exogenous alpha-sarcin to these same lysates results in cleavage of the 26 S rRNA of the 60 S ribosomal subunit, characteristic of the cytotoxic action of alpha-sarcin. We conclude that A. giganteus ribosomes are not inherently resistant to the action of alpha-sarcin but are protected in vivo by producing alpha-sarcin in an inactive form and/or by the efficient cotranslational secretion of the toxin.