The product of the lon gene in Escherichia coli, protease La, plays an important role in the degradation of abnormal proteins. To determine whether the presence of abnormal proteins stimulates expression of this gene, we examined its transcription using a lon-lacZ operon fusion. After the cells synthesized large amounts of aberrant polypeptides (e.g. following incorporation of the arginine analog, canavanine, or production of incomplete proteins with puromycin, or induction of translational errors with streptomycin), these cells showed a two- to threefold increase in lon--lacZ expression. Furthermore, synthesis of a single cloned protein, e.g. human tissue plasminogen activator, caused a similar increase in lon transcription. This induction of lon by abnormal proteins requires the heat shock regulatory gene htpR and was not seen in htpR- cells. Under these various conditions, other heat shock proteins were also induced. Thus, the appearance of aberrant cell proteins may be a common signal under many adverse conditions for the induction of cell protease (or proteases) and other heat shock proteins.