In a mouse model, cell-mediated immunity to Coccidioides immitis, as assayed by the delayed hypersensitivity skin test, was transferred with whole immunogenic RNA extract and its greater than 33S and 6S-13S sedimentation fractions. Both fractions were cleaved by RNase, but the products retained their transfer activity. The greater than 33S fraction of immunogenic RNA extract was inactivated by pronase, whereas the 6S-13S fraction was resistant to the proteolytic enzyme; however, after RNase treatment the latter fraction was sensitive to pronase. This finding suggests a protective role for RNA. Dialysis of immunogenic RNA extract yielded a dialysate with a ratio of absorbance at 260 nm to that at 280 nm (A260:A280) of 1.02. Similarly, the dialysis product of RNase-treated RNA is active and has an A260:A280 ratio of 1.34. The data indicate that at least part of the active moiety of immunogenic RNA extracts is an RNA-associated, pronase-labile peptide or nucleopeptide. Furthermore, it is possible that the dialyzable transfer factor may be the same peptide or nucleopeptide cleaved from immunogenic RNA during preparation of the transfer factor.