88 clinical isolates of gram-negative bacilli (23 Enterobacter, 23 Klebsiella, 21 E. coli, and 21 Pseudomonas) all showed susceptibility to one or more cephalosporins and were nitrocefin test negative. When cultured overnight in the presence of 1, 10, or 100 mg/l of cefotaxime, 19 Enterobacter strains grew beta-lactamase-producing variants, 15 of them at concentrations less than or equal to 10 mg/l of cefotaxime. All enzyme-producing variants showed resistance to a number of cephalosporins including non-hydrolyzable cephalosporins and other beta-lactam antibiotics, except mecillinam and thienamycin. With the other gram-negative bacilli resistant mutants did not emerge in the presence of cefotaxime. These findings are discussed in relation to use of third generation cephalosporins as first hand monotherapy in patients.