With partially purified kidney dehydropeptidase-I (DHP-I) preparations, the hydrolysis kinetics of glycyldehydrophenylalanine (Gly-dPh) by DHP-I were found to be completely non-Michaelian, whereas those of PS-5 and imipenem were composed of at least two-phase reactions which were also observed using Bacillus cereus type II beta-lactamase. Thus the DHP-I stabilities of 34 PS-5 carbapenem derivatives which were synthesized by chemical modification at the C-3 side chain of PS-5 were examined in vitro using fresh mouse, dog and human DHP-I preparations, and are tentatively expressed in reference to the DHP-I stabilities of PS-5. The in vitro DHP-I stability of PS-5 was significantly improved by introduction of basic side chains and cysteines at C-3. More particularly, the D-cysteinyl side chain was more stable relative to DHP-I than the L-cysteinyl. In vivo, however, the degree of improvement of the DHP-I-stability by chemical modification at C-3 was not sufficient enough to establish therapeutically effective levels of serum concentrations and urinary recoveries of the carbapenem derivatives after parenteral administration.