This invention provides novel caspase inhibitors of formula I: ##STR00001## wherein R.sup.1 is hydrogen, CHN.sub.2, R, or --CH.sub.2Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R.sup.2 is CO.sub.2H, CH.sub.2CO.sub.2H, or esters, amides or isosteres thereof; X.sub.2--X.sub.1 is N(R.sup.3)--C(R.sup.3), C(R.sup.3).sub.2--C(R.sup.3), C(R.sup.3).sub.2--N, N.dbd.C, C(R.sup.3).dbd.C, C(.dbd.O)--N, or C(.dbd.O)--C(R.sup.3); each R.sup.3 is independently selected from hydrogen or C.sub.1-6 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by .dbd.O, or one or more halogen, C.sub.1-4 alkyl, or C.sub.1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.