A recombinant human interleukin-6 mutant with enhanced conformational stability toward denaturant was obtained by site-specific mutagenesis. The clone was identified as having a single amino acid substitution of Lys70-->Glu. When urea-induced denaturation was monitored by the change in fluorescence intensity at 360 nm, Lys70-->Glu mutation shifted the midpoint of unfolding transition from 5.8 M (wild type) to 6.6 M urea. This mutation did not impair the biological activity.