Partially reduced interferon-a ($IFN-{alpha}$) was cross-linked with thymosin ${alpha}1$ ($T{alpha}1$) using sulfo-succinimidyl (4-iodoacetyl) amino benzoate (SIAB), a bifunctional cross-linking reagent. The partially reduced $IFN-{alpha}$ optimal for the cross-linking reaction was obtained by incubating native $IFN-{alpha}$ with 0.5 mM DTT at $30^{circ}C$ for 60~100 min. $T{alpha}1$ was activated by incubating with sulfo-SIAB at $37^{circ}C$ for 30 min to produce $T{alpha}1-IAB$. The $T{alpha}1-IFN-{alpha}$ cross-linking was achieved by the reaction of the partially reduced $IFN-{alpha}$ with $T{alpha}1-IAB$. This cross-linking was between the sulfhydryl group of Cys1 in $IFN-{alpha}$ and the N-terminal amino group of $T{alpha}1$ through acetyl amino benzoate as a spacer. The immunological activity of the cross-linked molecule showed the same extent as that of $T{alpha}1$, and most of the antiviral activity was retained compared to that of the partially reduced $IFN-{alpha}$.