A- 770041 is a src-family selective lck inhibitor with greater than 90% inhibition of IL-2 in vivo at 8 h when dosed at ED90 in mice and rats. A-770041 is greater than 300-fold selective against fyn, the other src-family kinase involved in T-cell signaling. A-770041 exhibits >60-fold selectivity versus the src-family members src and fgr, and >8-fold versus lyn and hck. Selectivity against the receptor tyrosine kinases tie-2 and kdr was >340-fold. In the anti-CD3 stimulated human whole blood assay, A-770041 inhibited IL-2 production with an IC50 of 0.08 uM. In rats, a correlation of concanavalin A-induced serum IL-2 levels to A-770041 concentrations was observed. Inhibition of IL-2 production was shown to be dependent upon in vivo plasma concentration of A-770041 with an in vivo EC50 of 0.078 uM. A-770041 represents the most selective lck inhibitor described to date and represents an advance not only in the understanding of structural features important for src-family selectivity, but also in the potential arsenal for the treatment of immunological conditions, in particular transplant rejection.