SummaryMulticopy plasmids that have been engineered to produce large quantitites of a single gratuitous (nonfunctional, non-toxic) protein are often problematic. When fully induced, these engineered constructions produce very sick bacteria. The reasons for this may be found in the physiology of wild-type laboratory strains that have been selected to grow at maximum rates with optimal quantities of their proteins. Such bacteria apparently experience the accumulation of gratuitous proteins as an internal shift down and they respond to this with a starvation response. Unlike the shift down associated with a change of growth media, the production of large quantities of gratuitous protein is not associated with a new preprogrammed steady-state of balanced growth. Consequently, the starvation response continues until the bacteria commit suicide by, among other things, destroying their ribosomes.