An inhibitor-resistant beta-lactamase (SHV-10), derived from an SHV-5 variant (SHV-9), was found in an Escherichia coli clinical isolate. In SHV-10, Ser-130 was replaced by Gly. The enzyme partially retained its ability to hydrolyze penicillins, but its activity against cephalosporins was drastically reduced. A Ser-130-->Gly mutant of the prototype SHV-5, obtained by site-directed mutagenesis, had properties similar to those of SHV-10.