This invention provides caspase inhibitors of formula I: wherein Z is oxygen or sulfur; R.sup.1 is hydrogen, --CHN.sub.2, R, CH.sub.2OR, CH.sub.2SR, or --CH.sub.2Y; between R.sup.3 and R.sup.4 represents a single or double bond; Y is an electronegative leaving group; R.sup.2 is CO.sub.2H, CH.sub.2CO.sub.2H, or esters, amides or isosteres thereof; R.sup.3is a group capable of fitting into the S2 subsite of a caspase enzyme; R.sup.4 is a hydrogen or C.sub.1-6 alkyl or R.sup.3 and R.sup.4 taken together form a ring; Ring A and Ring B are each heterocyclic rings, and R and R.sup.5 are as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1.beta. secretion.